)| PMID |
18488224 ( ) |
|---|---|
| Title | NOX enzymes and diabetic complications. |
| Abstract | Several molecular mechanisms have been identified that mediate the tissue-damaging effects of hyperglycemia. These are increased flux through the polyol and hexosamine pathways, increased formation of advanced glycation end products, activation of protein kinase C, and augmented generation of reactive oxygen species (ROS). Increased production of ROS not only causes cellular damage but also activates the signal transduction cascade that activates specific target genes. Based on recent experimental data, it is now accepted that increased NADPH oxidase activity in tissues vulnerable to hyperglycemia takes place downstream of the advanced glycation end products and protein kinase C pathways, two of the primary mechanisms involved in the pathogenesis of diabetic complications. Thus, compounds that suppress NADPH oxidase activity may offer therapeutic benefits to ameliorate diabetic complications, highlighting the significance of NADPH oxidase as a new therapeutic target. |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | 80 | Nox5 | nadph oxidase | NOX5 | |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | 49 | angiotensin ii | ang ii | Ang | |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | 28 | plasminogen activator inhibitor 1 | pai 1 | PAI-1 | |
| 7891 | NOX4 | NADPH oxidase 4 | 28 | Nox4-containing | Nox4-derived | NOX4 | |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | 24 | p22 phox | |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | 22 | Nox2 | NOX2 | gp91 phox | |
| 7889 | NOX1 | NADPH oxidase 1 | 19 | NOX1 | Nox1-containing | |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | 18 | monocyte chemoattractant protein 1 | mcp 1 | MCP-1 | |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | 17 | p47 | |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | 16 | ERK | p40 | MAPK | p38 | ERK2 | |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | 13 | Rac | Akt | PKB | protein kinase b | |
| 8824 | SERPINF1 | serpin peptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 1 | 8 | PEDF | |
| 6204 | JUN | jun oncogene | 6 | AP-1 | c jun | c-Jun | |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | 6 | caspase 3 | |
| 12680 | VEGFA | vascular endothelial growth factor A | 6 | VEGF | VEGF-induced | vegf a | |
| 6877 | MAPK3 | mitogen-activated protein kinase 3 | 6 | ERK1 | |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | 5 | chronic granulomatous disease | p67 phox | |
| 9393 | PRKCA | protein kinase C, alpha | 5 | protein kinase c | |
| 4141 | GAPDH | glyceraldehyde-3-phosphate dehydrogenase | 5 | GAPDH | glyceraldehyde 3 phosphate dehydrogenase | |
| 6881 | MAPK8 | mitogen-activated protein kinase 8 | 4 | JNK | |
| 3796 | FOS | v-fos FBJ murine osteosarcoma viral oncogene homolog | 4 | ap 1 | |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 4 | tumor necrosis factor | TNF-_amp_#945 | |
| 399 | ALB | albumin | 4 | albumin | |
| 613 | APOE | apolipoprotein E | 4 | apoE | |
| 11998 | TP53 | tumor protein p53 | 3 | p53 | |
| 6081 | INS | insulin | 3 | insulin | |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | 3 | osteopontin | |
| 1516 | CAT | catalase | 3 | catalase | |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | 3 | ACE | angiotensin converting enzyme | |
| 2197 | COL1A1 | collagen, type I, alpha 1 | 3 | collagen | |
| 6554 | LEPR | leptin receptor | 2 | leptin receptor | Lepr | |
| 8799 | PDGFA | platelet-derived growth factor alpha polypeptide | 2 | PDGF | |
| 7890 | NOX3 | NADPH oxidase 3 | 2 | Nox3 | |
| 11765 | TGFA | transforming growth factor, alpha | 2 | transforming growth factor | |
| 5006 | HMGCR | 3-hydroxy-3-methylglutaryl-Coenzyme A reductase | 1 | 3 hydroxy 3 methylglutaryl coenzyme a reductase | |
| 6318 | KIF2A | kinesin heavy chain member 2A | 1 | HK-2 | |
| 30802 | PNPLA2 | patatin-like phospholipase domain containing 2 | 1 | pigment epithelium derived factor | |
| 11820 | TIMP1 | TIMP metallopeptidase inhibitor 1 | 1 | TIMP-1 | |
| 8800 | PDGFB | platelet-derived growth factor beta polypeptide (simian sarcoma viral (v-sis) oncogene homolog) | 1 | platelet derived growth factor | |
| 3176 | EDN1 | endothelin 1 | 1 | endothelin 1 | |
| 381 | AKR1B1 | aldo-keto reductase family 1, member B1 (aldose reductase) | 1 | aldose reductase | |
| 2244 | COQ7 | coenzyme Q7 homolog, ubiquinone (yeast) | 1 | coenzyme q | |
| 6876 | MAPK14 | mitogen-activated protein kinase 14 | 1 | p38 mitogen activated protein kinase | |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | 1 | interleukin 6 | |
| 2202 | COL4A1 | collagen, type IV, alpha 1 | 1 | collagen iv | |
| 9071 | PLG | plasminogen | 1 | plasminogen | |
| 11283 | SRC | v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) | 1 | c src | |
| 11416 | STN | statin | 1 | statin | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 1 | SOD | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 4141 | GAPDH | glyceraldehyde-3-phosphate dehydrogenase | GAPDH | 1.6 | activity of the key glycolytic enzyme glyceraldehyde-3 phosphate dehydrogenase (GAPDH) GAPDH |
| 4141 | GAPDH | glyceraldehyde-3-phosphate dehydrogenase | GAPDH | 1.6 | Under decreased GAPDH activity all the glycolytic intermediates upstream of GAPDH overflow which |
| 4141 | GAPDH | glyceraldehyde-3-phosphate dehydrogenase | GAPDH | 1.6 | Under decreased GAPDH activity all the glycolytic intermediates upstream of GAPDH overflow which activates such bypasses as the polyol pathway and |
| 4141 | GAPDH | glyceraldehyde-3-phosphate dehydrogenase | GAPDH | 1.6 | The increased level of the substrate of GAPDH glyceraldehyde-3 phosphate leads to overproduction of methylglyoxal the major intracellular |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 1.3 | various factors associated with diabetic conditions including angiotensin II (Ang Ang II aldosterone endothelin-1 platelet-derived growth factor (PDGF), PDGF TGF-_amp_#946 and |
| 8799 | PDGFA | platelet-derived growth factor alpha polypeptide | PDGF | 1.2 | II (Ang Ang II aldosterone endothelin-1 platelet-derived growth factor (PDGF), PDGF TGF-_amp_#946 and tumor necrosis factor-_amp_#945 (TNF-_amp_#945;) TNF-_amp_#945 enhance the expression |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-_amp_#945 | 1.2 | growth factor (PDGF), PDGF TGF-_amp_#946 and tumor necrosis factor-_amp_#945 (TNF-_amp_#945;) TNF-_amp_#945 enhance the expression and activity of NADPH oxidase the involvement |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | Nox2 | 0.5 | enzyme consisting of the membrane-bound catalytic subunit gp91 phox (Nox2) Nox2 and p22 phox which associate with regulatory cytosolic subunits p47 |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 1.0 | of the membrane-bound catalytic subunit gp91 phox (Nox2) Nox2 and p22 phox which associate with regulatory cytosolic subunits p47 phox p67 |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | Nox2 and p22 phox which associate with regulatory cytosolic subunits p47 phox p67 phox p40 phox and Rac during the process |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 | 1.6 | p22 phox which associate with regulatory cytosolic subunits p47 phox p67 phox p40 phox and Rac during the process of enzyme |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | p40 | 3.2 | which associate with regulatory cytosolic subunits p47 phox p67 phox p40 phox and Rac during the process of enzyme activation |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Rac | 1.8 | regulatory cytosolic subunits p47 phox p67 phox p40 phox and Rac during the process of enzyme activation |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | Nox2 | 0.5 | Recently numerous homologs of Nox2 including Nox1 Nox3 Nox4 and Nox5 have been identified in |
| 7889 | NOX1 | NADPH oxidase 1 | Nox1 | 1.4 | Recently numerous homologs of Nox2 including Nox1 Nox3 Nox4 and Nox5 have been identified in nonphagocytic cells |
| 7890 | NOX3 | NADPH oxidase 3 | Nox3 | 1.4 | Recently numerous homologs of Nox2 including Nox1 Nox3 Nox4 and Nox5 have been identified in nonphagocytic cells |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 3.9 | Recently numerous homologs of Nox2 including Nox1 Nox3 Nox4 and Nox5 have been identified in nonphagocytic cells |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | NOX5 | 0.9 | Recently numerous homologs of Nox2 including Nox1 Nox3 Nox4 and Nox5 have been identified in nonphagocytic cells |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | Nox5 | 0.9 | Recently numerous homologs of Nox2 including Nox1 Nox3 Nox4 and Nox5 have been identified in nonphagocytic cells |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | Nox2 | 0.5 | Among these isoforms the expression of Nox2 Nox4 and Nox1 are identified in the target organs of |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 3.9 | Among these isoforms the expression of Nox2 Nox4 and Nox1 are identified in the target organs of diabetic |
| 7889 | NOX1 | NADPH oxidase 1 | NOX1 | 1.4 | Among these isoforms the expression of Nox2 Nox4 and Nox1 are identified in the target organs of diabetic |
| 7889 | NOX1 | NADPH oxidase 1 | Nox1 | 1.4 | Among these isoforms the expression of Nox2 Nox4 and Nox1 are identified in the target organs of diabetic complications including |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 1.0 | displayed an increased ROS level accompanied by the upregulation of p22 phox and p47 phox in the affected arteries 20 |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | ROS level accompanied by the upregulation of p22 phox and p47 phox in the affected arteries 20 |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | Nox2 | 0.5 | Abundant expression of Nox2 is documented in human atherosclerotic plaques 21 and expression levels |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | Nox2 | 0.5 | documented in human atherosclerotic plaques 21 and expression levels of Nox2 and p22 phox in human coronary arteries correlated with the |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 1.0 | human atherosclerotic plaques 21 and expression levels of Nox2 and p22 phox in human coronary arteries correlated with the severity of |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | Nox2 | 0.5 | Double knockout mice lacking apoE and Nox2 showed no improvement in the lesion area when compared with |
| 613 | APOE | apolipoprotein E | apoE | 0.1 | Double knockout mice lacking apoE and Nox2 showed no improvement in the lesion area when |
| 613 | APOE | apolipoprotein E | apoE | 0.0 | showed no improvement in the lesion area when compared with apoE knockout mice 24 |
| 7889 | NOX1 | NADPH oxidase 1 | Nox1 | 1.4 | To investigate the role of Nox1 in the development of atherosclerosis we recently generated double knockout |
| 7889 | NOX1 | NADPH oxidase 1 | Nox1 | 1.4 | atherosclerosis we recently generated double knockout mice lacking apoE and Nox1 |
| 613 | APOE | apolipoprotein E | apoE | 0.1 | development of atherosclerosis we recently generated double knockout mice lacking apoE and Nox1 |
| 613 | APOE | apolipoprotein E | apoE | 0.0 | aortic sinus no difference was observed between double knockout and apoE knockout mice (Matsuno, Matsuno unpublished data |
| 7889 | NOX1 | NADPH oxidase 1 | Nox1 | 1.4 | results hence provide no evidence for the involvement of the Nox1 isoform in the development of atherosclerosis |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 0.9 | safety of pharmacological interventions including antivascular endothelial growth factor (VEGF) VEGF therapy have not been fully proven |
| 7889 | NOX1 | NADPH oxidase 1 | Nox1 | 1.4 | Expression of the catalytic subunit of NADPH oxidase Nox1 along with other membrane and cytosolic subunits p22 phox p47 |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 1.0 | NADPH oxidase Nox1 along with other membrane and cytosolic subunits p22 phox p47 phox and p67 phox was documented in a |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | Nox1 along with other membrane and cytosolic subunits p22 phox p47 phox and p67 phox was documented in a cultured cell |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 | 1.6 | other membrane and cytosolic subunits p22 phox p47 phox and p67 phox was documented in a cultured cell line established from |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 1.0 | functional similarities to pericytes isolated from the retina and upregulate p22 phox when exposed to high glucose or Ang II 27 |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 1.3 | and upregulate p22 phox when exposed to high glucose or Ang II 27 |
| 6204 | JUN | jun oncogene | c-Jun | 0.8 | The activation of PKC-_amp_#948 and increased c-Jun N-terminal kinase (JNK) JNK phosphorylation was demonstrated in cells under |
| 6881 | MAPK8 | mitogen-activated protein kinase 8 | JNK | 1.5 | The activation of PKC-_amp_#948 and increased c-Jun N-terminal kinase (JNK) JNK phosphorylation was demonstrated in cells under cyclic stretch |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | Immunoprecipitation and immunoblot analyses showed rapid association of PKC-_amp_#948 with p47 phox in these cells and inhibitors of NADPH oxidase diphenylene |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | is thought to act by interfering with the binding of p47 phox to Nox2 |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | Nox2 | 0.5 | act by interfering with the binding of p47 phox to Nox2 |
| 6881 | MAPK8 | mitogen-activated protein kinase 8 | JNK | 1.5 | As the introduction of dominant-negative PKC-_amp_#948 or an inhibitor of JNK prevented stretch-induced apoptosis involvement of the PKC-_amp_#948 _amp_#8211 NADPH oxidase_amp_#8211 |
| 6881 | MAPK8 | mitogen-activated protein kinase 8 | JNK | 1.5 | prevented stretch-induced apoptosis involvement of the PKC-_amp_#948 _amp_#8211 NADPH oxidase_amp_#8211 JNK cascade was suggested in the apoptotic changes in pericytes under |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 0.9 | been shown to elicit an angiogenic response by production of VEGF a potent growth factor that stimulates proliferation migration and tube |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | cells exposed to AGEs the translocation of PKC-_amp_#946 2 and p47 phox was observed and the inhibition of PKC totally suppressed |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | and the inhibition of PKC totally suppressed AGE-mediated translocation of p47 phox and ROS generation 29 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF-induced | 0.9 | corroborated the finding that ROS derived from NADPH oxidase modulate VEGF-induced angiogenesis 30 |
| 8824 | SERPINF1 | serpin peptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 1 | PEDF | 1.3 | Pigment epithelium-derived factor (PEDF), PEDF a glycoprotein that belongs to the superfamily of serine protease |
| 8824 | SERPINF1 | serpin peptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 1 | PEDF | 1.3 | The amount of PEDF produced by retinal cells was positively correlated with oxygen concentrations |
| 8824 | SERPINF1 | serpin peptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 1 | PEDF | 1.3 | It is interesting to note that PEDF levels in ocular fluids are decreased in diabetic patients with |
| 8824 | SERPINF1 | serpin peptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 1 | PEDF | 1.3 | patients with proliferative retinopathy 34 suggesting that the loss of PEDF may contribute to the development of proliferative retinopathy |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 0.9 | study the intravenous administration of AGEs stimulated the expression of VEGF messenger ribonucleic acid (mRNA) mRNA in the eye while simultaneous |
| 8824 | SERPINF1 | serpin peptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 1 | PEDF | 1.3 | acid (mRNA) mRNA in the eye while simultaneous treatments with PEDF suppressed the upregulation of VEGF induced by AGEs 35 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 0.9 | eye while simultaneous treatments with PEDF suppressed the upregulation of VEGF induced by AGEs 35 |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 1.0 | In the eye of AGE-treated rats mRNA levels of both p22 phox and Nox2 were significantly elevated while PEDF treatments suppressed |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | Nox2 | 0.5 | of AGE-treated rats mRNA levels of both p22 phox and Nox2 were significantly elevated while PEDF treatments suppressed this upregulation |
| 8824 | SERPINF1 | serpin peptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 1 | PEDF | 1.3 | of both p22 phox and Nox2 were significantly elevated while PEDF treatments suppressed this upregulation |
| 8824 | SERPINF1 | serpin peptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 1 | PEDF | 1.3 | in the retina is augmented by AGEs and blocked by PEDF |
| 8824 | SERPINF1 | serpin peptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 1 | PEDF | 1.3 | It remains to be clarified however how PEDF affects the expression of NADPH oxidase subunits in the eye |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | PAI-1 | 1.8 | by transforming growth factor-_amp_#946 ( TGF-_amp_#946 plasminogen activator inhibitor-1 ( PAI-1 p53 caspase-3 monocyte chemoattractant protein-1 ( MCP-1 osteopontin and nitric |
| 11998 | TP53 | tumor protein p53 | p53 | 1.7 | transforming growth factor-_amp_#946 ( TGF-_amp_#946 plasminogen activator inhibitor-1 ( PAI-1 p53 caspase-3 monocyte chemoattractant protein-1 ( MCP-1 osteopontin and nitric oxide |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | MCP-1 | 1.6 | activator inhibitor-1 ( PAI-1 p53 caspase-3 monocyte chemoattractant protein-1 ( MCP-1 osteopontin and nitric oxide ( NO |
| 8799 | PDGFA | platelet-derived growth factor alpha polypeptide | PDGF | 1.2 | The growth factors and cytokines elevated under hyperglycemia TGF-_amp_#946 PDGF TNF-_amp_#945 PAI-1 and monocyte chemoattractant protein-1 (MCP-1) MCP-1 induce mesangial |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-_amp_#945 | 1.2 | The growth factors and cytokines elevated under hyperglycemia TGF-_amp_#946 PDGF TNF-_amp_#945 PAI-1 and monocyte chemoattractant protein-1 (MCP-1) MCP-1 induce mesangial expansion |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | PAI-1 | 1.8 | growth factors and cytokines elevated under hyperglycemia TGF-_amp_#946 PDGF TNF-_amp_#945 PAI-1 and monocyte chemoattractant protein-1 (MCP-1) MCP-1 induce mesangial expansion by |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | MCP-1 | 1.6 | hyperglycemia TGF-_amp_#946 PDGF TNF-_amp_#945 PAI-1 and monocyte chemoattractant protein-1 (MCP-1) MCP-1 induce mesangial expansion by accumulating ECM components in the glomerular |
| 2197 | COL1A1 | collagen, type I, alpha 1 | collagen | 0.3 | key mediator of ECM accumulation and augments the expression of collagen types I III IV and fibronectin in cultured human and |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 1.3 | Along with hemodynamic effects Ang II stimulates the synthesis of ECM components by acting on |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 1.3 | While a clear link between Ang II-induced ROS production and hypertrophy of MCs was documented 52 |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 1.3 | that the production of mesangial ECM components is augmented by Ang II via the upregulation of TGF-_amp_#946 53 |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | PAI-1 | 1.8 | systems correlate with each other 55 56 given that increased PAI-1 in renal diseases prevents the activation of MMPs and the |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | PAI-1 | 1.8 | Previous studies confirmed that MMPs TIMP and PAI-1 are regulated by high glucose |
| 11820 | TIMP1 | TIMP metallopeptidase inhibitor 1 | TIMP-1 | 1.1 | ECM metabolism in MCs are associated with ROS-stimulated upregulation of TIMP-1 |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | PAI-1 | 1.8 | inhibited both high glucose- and H 2 O 2 -induced PAI-1 upregulation 58 59 |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | PAI-1 | 1.8 | suggest that ROS mediate both high glucose- and TGF-_amp_#946 1-induced PAI-1 expression and qualify ROS as intracellular messengers that play a |
| 6318 | KIF2A | kinesin heavy chain member 2A | HK-2 | 0.3 | In human tubular proximal cells (HK-2 HK-2 cells hyperglycemia induces apoptotic changes via an increase in oxidative |
| 11998 | TP53 | tumor protein p53 | p53 | 1.7 | cells ROS production and expressions of proapoptotic genes such as p53 Bax and caspase-3 are attenuated along with reduced proximal tubular |
| 6554 | LEPR | leptin receptor | Lepr | 1.3 | as well as in a type 2 model with obesity Lepr db/db db db (db/db) db db mice |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 1.3 | Besides glucose-induced generation of ROS Ang II-induced generation of ROS is also documented to induce apoptosis |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | PAI-1 | 1.8 | ROS and inflammation Similar to TGF-_amp_#946 1 and PAI-1 mentioned above ROS upregulate various chemokines including MCP-1 osteopontin migration |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | MCP-1 | 1.6 | 1 and PAI-1 mentioned above ROS upregulate various chemokines including MCP-1 osteopontin migration inhibitory factor and monocyte colony-stimulating factor which amplify |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | MCP-1 | 1.6 | MCP-1 recruits monocytes and lymphocytes and induces glomerular and interstitial inflammation |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | MCP-1 | 1.6 | podocytes ROS have been shown to mediate the expression of MCP-1 induced by high glucose TNF-_amp_#945 TGF-_amp_#946 and AGEs through the |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-_amp_#945 | 1.2 | to mediate the expression of MCP-1 induced by high glucose TNF-_amp_#945 TGF-_amp_#946 and AGEs through the activation of nuclear factor-kappaB (NF-_amp_#954;B) |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 3.9 | the catalytic subunits localized in the membrane the expression of Nox4 initially cloned and identified in the kidney is abundant in |
| 7889 | NOX1 | NADPH oxidase 1 | Nox1 | 1.4 | Nox1 and Nox2 were similarly detected in the adult rat kidney |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 0.5 | Nox1 and Nox2 were similarly detected in the adult rat kidney |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | Nox2 | 0.5 | Nox1 and Nox2 were similarly detected in the adult rat kidney but at |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 3.9 | Based on its high expression in renal tissue Nox4 has been assumed to play a major role in the |
| 7889 | NOX1 | NADPH oxidase 1 | Nox1 | 1.4 | recent reports as mentioned below which suggest the association of Nox1 and Nox2 with the pathogenesis of diabetic nephropathy |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 0.5 | recent reports as mentioned below which suggest the association of Nox1 and Nox2 with the pathogenesis of diabetic nephropathy |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | Nox2 | 0.5 | as mentioned below which suggest the association of Nox1 and Nox2 with the pathogenesis of diabetic nephropathy |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 1.3 | These Nox isoforms are upregulated by multiple factors including Ang II AGEs and a high-salt diet associated with the metabolic |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 1.3 | High glucose ( HG Ang II and AGEs elicit activation of PKC and NADPH oxidase |
| 6204 | JUN | jun oncogene | AP-1 | 1.1 | turn on signal transduction cascades and two master transcription factors AP-1 and NF-_amp_#954 B leading to the up-regulation of TGF-_amp_#946 PAI-1 |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | PAI-1 | 1.8 | AP-1 and NF-_amp_#954 B leading to the up-regulation of TGF-_amp_#946 PAI-1 and MCP-1 involved in the ECM turnover and the development |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | MCP-1 | 1.6 | NF-_amp_#954 B leading to the up-regulation of TGF-_amp_#946 PAI-1 and MCP-1 involved in the ECM turnover and the development of renal |
| 6877 | MAPK3 | mitogen-activated protein kinase 3 | ERK1 | 1.7 | ERK1/2 ERK1 2 extracellular signal-regulated kinases 1 and 2 Akt/PKB Akt PKB |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 1.8 | ERK1/2 ERK1 2 extracellular signal-regulated kinases 1 and 2 Akt/PKB Akt PKB Akt/protein Akt protein kinase B AP-1 activated protein-1 NF-_amp_#954 |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | PKB | 1.8 | ERK1 2 extracellular signal-regulated kinases 1 and 2 Akt/PKB Akt PKB Akt/protein Akt protein kinase B AP-1 activated protein-1 NF-_amp_#954 B |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 1.8 | extracellular signal-regulated kinases 1 and 2 Akt/PKB Akt PKB Akt/protein Akt protein kinase B AP-1 activated protein-1 NF-_amp_#954 B nuclear factor-kappaB |
| 6204 | JUN | jun oncogene | AP-1 | 1.1 | and 2 Akt/PKB Akt PKB Akt/protein Akt protein kinase B AP-1 activated protein-1 NF-_amp_#954 B nuclear factor-kappaB MMP matrix metalloproteinases |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 1.3 | hyperglycemia db/db db db leptin receptor-deficient type 2 diabetic model Ang II angiotensin II-induced hypertension model SHR spontaneously hypertensive rat DS |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 3.9 | Nox4 Nox4 is broadly distributed in the kidney including glomeruli and |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 3.9 | Nox4 Nox4 is broadly distributed in the kidney including glomeruli and nephron |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 3.9 | The level of Nox4 mRNA increases in distal tubular cells and glomeruli in STZ-induced |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 3.9 | The increased level of Nox4 is recovered by insulin treatment 84 |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 3.9 | The expression of Nox4 is verified in MCs and Nox4-derived ROS was documented to |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4-derived | 1.4 | The expression of Nox4 is verified in MCs and Nox4-derived ROS was documented to mediate Ang II-induced signaling and protein |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 1.3 | verified in MCs and Nox4-derived ROS was documented to mediate Ang II-induced signaling and protein synthesis by the activation of extracellular |
| 6877 | MAPK3 | mitogen-activated protein kinase 3 | ERK1 | 1.7 | the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/ERK2) ERK1 ERK2 85 86 |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | ERK2 | 3.2 | activation of extracellular signal-regulated kinases 1 and 2 (ERK1/ERK2) ERK1 ERK2 85 86 |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 3.9 | 2 diabetic model immunohistochemical analyses suggested an increased expression of Nox4 protein and in fact a concomitant increase in Nox4 mRNA |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 3.9 | of Nox4 protein and in fact a concomitant increase in Nox4 mRNA was depicted by a quantitative method 87 |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 3.9 | in accord with the study demonstrating that the downregulation of Nox4 by the systemic administration of antisense oligonucleotides attenuates the generation |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 3.9 | Thus a correlation between ROS derived from Nox4 and renal hypertrophy is clearly indicated |
| 7889 | NOX1 | NADPH oxidase 1 | Nox1 | 1.4 | Nox1 It is interesting to note that Nox1 is identified as |
| 7889 | NOX1 | NADPH oxidase 1 | Nox1 | 1.4 | Nox1 It is interesting to note that Nox1 is identified as a potential candidate gene implicated in diabetic |
| 7889 | NOX1 | NADPH oxidase 1 | Nox1 | 1.4 | The study showed that the Nox1 gene is located in the linkage regions along with p22 |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 1.0 | Nox1 gene is located in the linkage regions along with p22 phox and Nox3 genes |
| 7890 | NOX3 | NADPH oxidase 3 | Nox3 | 1.4 | located in the linkage regions along with p22 phox and Nox3 genes |
| 7889 | NOX1 | NADPH oxidase 1 | Nox1 | 1.4 | findings remains to be answered by elucidating the role of Nox1 in renal embryogenesis and physiology in humans |
| 7889 | NOX1 | NADPH oxidase 1 | Nox1 | 1.4 | Although ROS derived from Nox1 have been implicated in Ang II-mediated hypertension 90 _amp_#8211 92 |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 1.3 | Although ROS derived from Nox1 have been implicated in Ang II-mediated hypertension 90 _amp_#8211 92 whether Nox1 in the kidney |
| 7889 | NOX1 | NADPH oxidase 1 | Nox1 | 1.4 | been implicated in Ang II-mediated hypertension 90 _amp_#8211 92 whether Nox1 in the kidney takes part in the development of hypertension |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 1.3 | Chabrashvili et al demonstrated that Ang II-infused mice promote oxidative stress in the renal cortex via |
| 7889 | NOX1 | NADPH oxidase 1 | Nox1 | 1.4 | stress in the renal cortex via increased mRNA expression of Nox1 and p22 phox but not of Nox4 93 |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 1.0 | the renal cortex via increased mRNA expression of Nox1 and p22 phox but not of Nox4 93 |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 3.9 | mRNA expression of Nox1 and p22 phox but not of Nox4 93 |
| 2197 | COL1A1 | collagen, type I, alpha 1 | collagen | 0.3 | exhibit a higher ratio of urinary protein excretion and cortical collagen content an increased renal cortical expression of Nox1 and p22 |
| 7889 | NOX1 | NADPH oxidase 1 | Nox1 | 1.4 | and cortical collagen content an increased renal cortical expression of Nox1 and p22 phox accompanied by the activation of ERK1/ERK2 ERK1 |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 1.0 | collagen content an increased renal cortical expression of Nox1 and p22 phox accompanied by the activation of ERK1/ERK2 ERK1 ERK2 was |
| 6877 | MAPK3 | mitogen-activated protein kinase 3 | ERK1 | 1.7 | Nox1 and p22 phox accompanied by the activation of ERK1/ERK2 ERK1 ERK2 was demonstrated 94 |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | ERK2 | 3.2 | and p22 phox accompanied by the activation of ERK1/ERK2 ERK1 ERK2 was demonstrated 94 |
| 7889 | NOX1 | NADPH oxidase 1 | Nox1-containing | 0.9 | More recently Nox1-containing NADPH oxidase was suggested in the modulation of renal oxidative |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | p38 | 3.2 | modulation of renal oxidative stress and redox-dependent signaling of c-Src p38 mitogen-activated protein kinase (MAPK), MAPK JNK and focal adhesion kinase |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 3.2 | and redox-dependent signaling of c-Src p38 mitogen-activated protein kinase (MAPK), MAPK JNK and focal adhesion kinase 95 |
| 6881 | MAPK8 | mitogen-activated protein kinase 8 | JNK | 1.5 | redox-dependent signaling of c-Src p38 mitogen-activated protein kinase (MAPK), MAPK JNK and focal adhesion kinase 95 |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | Nox2 | 0.5 | Nox2 The localization of Nox2 is ascertained in podocytes glomeruli distal |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | Nox2 | 0.5 | Nox2 The localization of Nox2 is ascertained in podocytes glomeruli distal tubules and in TAL |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 3.9 | Aside from the preceding findings on Nox4 in the diabetic model the expression of Nox2 and enhanced |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | Nox2 | 0.5 | findings on Nox4 in the diabetic model the expression of Nox2 and enhanced membrane translocation of p47 phox were reported in |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | model the expression of Nox2 and enhanced membrane translocation of p47 phox were reported in the kidney of STZ-induced diabetic rats |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | Similarly increased NADPH oxidase activity and increased expressions of p47 phox Nox2 and Nox4 mRNA levels in the renal cortex |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | Nox2 | 0.5 | increased NADPH oxidase activity and increased expressions of p47 phox Nox2 and Nox4 mRNA levels in the renal cortex were observed |
| 7891 | NOX4 | NADPH oxidase 4 | NOX4 | 3.9 | increased NADPH oxidase activity and increased expressions of p47 phox Nox2 and Nox4 mRNA levels in the renal cortex were observed |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 3.9 | oxidase activity and increased expressions of p47 phox Nox2 and Nox4 mRNA levels in the renal cortex were observed in STZ-induced |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | Nox2 | 0.5 | generation of superoxide accompanied by enhanced renal cortical expression of Nox2 and p47 phox was also depicted in rats on a |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | superoxide accompanied by enhanced renal cortical expression of Nox2 and p47 phox was also depicted in rats on a high-salt diet |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | Nox2 | 0.5 | diabetic rat kidney through the upregulation of membrane expression of Nox2 and p47 phox |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | kidney through the upregulation of membrane expression of Nox2 and p47 phox |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | Nox2 | 0.5 | The upregulation of Nox2 and other cytosolic subunits in the renal cortex is also |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 3.2 | The cross-talk of NADPH oxidase with PKC and MAPK cascades has also been extensively studied |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | As PKC is implicated in the phosphorylation of p47 phox that organizes the translocation of other cytosolic subunits to |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | delineate the specificity of the _amp_#946 isoform the phosphorylation of p47 phox by other PKC isoforms was further characterized in a |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | and _amp_#950 isoforms expressed in human neutrophils can individually phosphorylate p47 phox and induce its translocation and ensuing activation of NADPH |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | reduction in NADPH oxidase activity accompanied by decreased expressions of p47 phox Nox2 and Nox4 mRNAs is demonstrated in the renal |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | Nox2 | 0.5 | NADPH oxidase activity accompanied by decreased expressions of p47 phox Nox2 and Nox4 mRNAs is demonstrated in the renal cortex suggesting |
| 7891 | NOX4 | NADPH oxidase 4 | NOX4 | 3.9 | NADPH oxidase activity accompanied by decreased expressions of p47 phox Nox2 and Nox4 mRNAs is demonstrated in the renal cortex suggesting |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 3.9 | activity accompanied by decreased expressions of p47 phox Nox2 and Nox4 mRNAs is demonstrated in the renal cortex suggesting that a |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 1.0 | (PKC-_amp_#945; PKC-_amp_#945 and PKC-_amp_#946 inhibitor G6976 suppresses increased expressions of p22 phox p47 phox and collagen IV along with reduced ROS |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | and PKC-_amp_#946 inhibitor G6976 suppresses increased expressions of p22 phox p47 phox and collagen IV along with reduced ROS production in |
| 2197 | COL1A1 | collagen, type I, alpha 1 | collagen | 0.3 | G6976 suppresses increased expressions of p22 phox p47 phox and collagen IV along with reduced ROS production in MCs under high |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 1.3 | Ang II acts as an important factor that initiates mesangial ECM |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 1.3 | In addition to its hemodynamic effects growth-stimulating signals driven by Ang II promote MC hypertrophy and ECM production |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 1.3 | Ang II elicits NADPH oxidase-dependent superoxide production in MCs and increases |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 1.3 | The activation of NADPH oxidase by Ang II is therefore suggested to be a PKC-dependent process in |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 1.3 | Subsequently Nox isoforms activated by Ang II in the kidney have been explored |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 3.9 | Nox4 is currently recognized as a target of Ang II since |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 1.3 | Nox4 is currently recognized as a target of Ang II since antisense oligonucleotides against Nox4 decrease Ang II-induced ROS |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 3.9 | as a target of Ang II since antisense oligonucleotides against Nox4 decrease Ang II-induced ROS production activation of Akt/PKB Akt PKB |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 1.3 | target of Ang II since antisense oligonucleotides against Nox4 decrease Ang II-induced ROS production activation of Akt/PKB Akt PKB and ERK1/2, |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 1.8 | against Nox4 decrease Ang II-induced ROS production activation of Akt/PKB Akt PKB and ERK1/2, ERK1 2 and protein synthesis in MCs |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | PKB | 1.8 | Nox4 decrease Ang II-induced ROS production activation of Akt/PKB Akt PKB and ERK1/2, ERK1 2 and protein synthesis in MCs 85 |
| 6877 | MAPK3 | mitogen-activated protein kinase 3 | ERK1 | 1.7 | II-induced ROS production activation of Akt/PKB Akt PKB and ERK1/2, ERK1 2 and protein synthesis in MCs 85 86 |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 1.3 | contrast to these findings there is a study demonstrating that Ang II infusion into rats augments oxidative stress and upregulates the |
| 7889 | NOX1 | NADPH oxidase 1 | Nox1 | 1.4 | augments oxidative stress and upregulates the renal cortical expression of Nox1 and p22 phox mRNAs but reduces the expression of Nox4 |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 1.0 | stress and upregulates the renal cortical expression of Nox1 and p22 phox mRNAs but reduces the expression of Nox4 via Ang |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 3.9 | Nox1 and p22 phox mRNAs but reduces the expression of Nox4 via Ang II type 1 receptor AT 1 93 |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 1.3 | p22 phox mRNAs but reduces the expression of Nox4 via Ang II type 1 receptor AT 1 93 |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | p38 | 3.2 | as second messengers to activate the signal transduction cascade via p38 MAPK and ERK |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 3.2 | second messengers to activate the signal transduction cascade via p38 MAPK and ERK |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | ERK | 3.2 | to activate the signal transduction cascade via p38 MAPK and ERK |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | p38 | 3.2 | inhibitor of NADPH oxidase DPI indeed inhibit the activation of p38 MAPK in MCs 110 |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 3.2 | of NADPH oxidase DPI indeed inhibit the activation of p38 MAPK in MCs 110 |
| 6204 | JUN | jun oncogene | AP-1 | 1.1 | two master transcription factors NF-_amp_#954 B and activated protein-1 (AP-1), AP-1 leading to the upregulation of respective target genes 42 |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | MCP-1 | 1.6 | Among these genes are fibrotic cytokines such as MCP-1 TGF-_amp_#946 and PAI-1 as well as ECM proteins including fibronectin |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | PAI-1 | 1.8 | these genes are fibrotic cytokines such as MCP-1 TGF-_amp_#946 and PAI-1 as well as ECM proteins including fibronectin and collagens |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | MCP-1 | 1.6 | Previous reports show that NF-_amp_#954 B regulates MCP-1 expression 69 while AP-1 mediates a high glucose-induced increase in |
| 6204 | JUN | jun oncogene | AP-1 | 1.1 | reports show that NF-_amp_#954 B regulates MCP-1 expression 69 while AP-1 mediates a high glucose-induced increase in TGF-_amp_#946 1 gene promoter |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | PAI-1 | 1.8 | was recognized in high glucose- and TGF-_amp_#946 1-induced upregulation of PAI-1 expression |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | PAI-1 | 1.8 | ROS while ROS mediate both high glucose- and TGF-_amp_#946 1-induced PAI-1 expression |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | PAI-1 | 1.8 | Increased PAI-1 then attenuates plasmin and MMP activity to perturb ECM degradation |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 1.8 | In STZ-induced diabetic rats the activation of Akt/protein Akt protein kinase B and ERK1/2 ERK1 2 was demonstrated downstream |
| 6877 | MAPK3 | mitogen-activated protein kinase 3 | ERK1 | 1.7 | the activation of Akt/protein Akt protein kinase B and ERK1/2 ERK1 2 was demonstrated downstream of Nox4-containing NADPH oxidase |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4-containing | 1.4 | kinase B and ERK1/2 ERK1 2 was demonstrated downstream of Nox4-containing NADPH oxidase |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 3.9 | Both kinases are activated under hyperglycemia and antisense oligonucleotides against Nox4 almost completely abrogate diabetes-induced activation of these kinases fibronectin expression |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 1.3 | Similar to Ang II-induced signaling Nox4 is again suggested as an upstream activator |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 3.9 | Similar to Ang II-induced signaling Nox4 is again suggested as an upstream activator of ERK1/2 ERK1 |
| 6877 | MAPK3 | mitogen-activated protein kinase 3 | ERK1 | 1.7 | Nox4 is again suggested as an upstream activator of ERK1/2 ERK1 2 and Akt/PKB, Akt PKB both critical for cell growth |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 1.8 | as an upstream activator of ERK1/2 ERK1 2 and Akt/PKB, Akt PKB both critical for cell growth and hypertrophy under hyperglycemia |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | PKB | 1.8 | an upstream activator of ERK1/2 ERK1 2 and Akt/PKB, Akt PKB both critical for cell growth and hypertrophy under hyperglycemia |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | p38 | 3.2 | by NADPH oxidase and leads to the activation of proapoptotic p38 MAPK and caspase-3 in cultured podocytes |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 3.2 | NADPH oxidase and leads to the activation of proapoptotic p38 MAPK and caspase-3 in cultured podocytes |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 3.9 | In cultured murine podocytes the expression of Nox4 and p22 phox mRNA was confirmed whereas the expression of |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 1.0 | In cultured murine podocytes the expression of Nox4 and p22 phox mRNA was confirmed whereas the expression of Nox2 was |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | Nox2 | 0.5 | and p22 phox mRNA was confirmed whereas the expression of Nox2 was documented in human cultured podocytes 113 |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | p38 | 3.2 | Podocyte apoptosis via p38 MAPK signaling was also demonstrated in TGF-_amp_#946 transgenic mice 114 |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 3.2 | Podocyte apoptosis via p38 MAPK signaling was also demonstrated in TGF-_amp_#946 transgenic mice 114 |
| 11998 | TP53 | tumor protein p53 | p53 | 1.7 | catalase in a kidney-specific manner the induction of proapoptotic genes p53 Bax and caspase-3 under STZ-induced diabetes was attenuated 63 |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | ACE | 0.6 | At present the blockade of RAS with angiotensin-converting enzyme (ACE) ACE inhibitors and Ang II receptor blockers (ARBs) ARBs is the |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 1.3 | blockade of RAS with angiotensin-converting enzyme (ACE) ACE inhibitors and Ang II receptor blockers (ARBs) ARBs is the most successful therapeutic |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | ACE | 0.6 | Since both ACE inhibitors and ARB suppress renal ROS production p47 phox expression |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | Since both ACE inhibitors and ARB suppress renal ROS production p47 phox expression and microalbuminuria in STZ-induced diabetic rats 117 the |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Rac | 1.8 | Besides their cholesterol-lowering effect statins inhibit Rac acylation thus perturbing the translocation of Rac to the membrane |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Rac | 1.8 | effect statins inhibit Rac acylation thus perturbing the translocation of Rac to the membrane fraction required for activation of NADPH oxidase |
| 7891 | NOX4 | NADPH oxidase 4 | NOX4 | 3.9 | albuminuria and mesangial expansion by minimizing oxidative stress via downregulating NOX4 expression in the kidney 87 |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 1.3 | High glucose- or Ang II-induced activation of MAPK in MCs was also completely blocked |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 3.2 | High glucose- or Ang II-induced activation of MAPK in MCs was also completely blocked by pitavastatin as well |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.3 | and aldosterone blockers indirectly suppress NADPH oxidase activity while an SOD mimetic tempol an antioxidant _amp_#945 -lipoic acid and apocynin directly |
| 9393 | PRKCA | protein kinase C, alpha | protein kinase c | 1.0 | these are increased flux through the polyol and hexosamine pathways increased formation of advanced glycation end products activation of protein kinase c and augmented generation of reactive oxygen species ros . |
| 9393 | PRKCA | protein kinase C, alpha | protein kinase c | 1.0 | based on recent experimental data it is now accepted that increased nadph oxidase activity in tissues vulnerable to hyperglycemia takes place downstream of the advanced glycation end products and protein kinase c pathways two of the primary mechanisms involved in the pathogenesis of diabetic complications. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | based on recent experimental data it is now accepted that increased nadph oxidase activity in tissues vulnerable to hyperglycemia takes place downstream of the advanced glycation end products and protein kinase c pathways two of the primary mechanisms involved in the pathogenesis |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | thus compounds that suppress nadph oxidase activity may offer therapeutic benefits to ameliorate diabetic complications highlighting the significance of nadph oxidase as a new therapeutic target. |
| 9393 | PRKCA | protein kinase C, alpha | protein kinase c | 1.0 | keywords atherosclerosis advanced glycation end products diabetes microvascular complications nadph oxidase protein kinase c |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | keywords atherosclerosis advanced glycation end products diabetes microvascular complications nadph oxidase protein kinase c |
| 9393 | PRKCA | protein kinase C, alpha | protein kinase c | 1.0 | other mechanisms identified later were augmentation of oxidative stress [ 2 ] increased formation of advanced glycation end products ages [ 3 ] and hyperglycemia induced activation of protein kinase c pkc isoforms [ 4 ]. |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | plasminogen activator inhibitor | 1.0 | pathway flux and ensuing modification of transcription factor proteins by n acetylglucosamine have been shown to induce abnormal expression of transforming growth factor _amp_#946; tgf _amp_#946; and plasminogen activator inhibitor pai 1 in renovascular tissues [ 5 ]. |
| 11765 | TGFA | transforming growth factor, alpha | transforming growth factor | 1.0 | more recently increased hexosamine pathway flux and ensuing modification of transcription factor proteins by n acetylglucosamine have been shown to induce abnormal expression of transforming growth factor _amp_#946; tgf _amp_#946; and plasminogen activator inhibitor pai 1 in renovascular tissues [ 5 ]. |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | pai 1 | 1.0 | ation of transcription factor proteins by n acetylglucosamine have been shown to induce abnormal expression of transforming growth factor _amp_#946; tgf _amp_#946; and plasminogen activator inhibitor pai 1 in renovascular tissues [ 5 ]. |
| 2244 | COQ7 | coenzyme Q7 homolog, ubiquinone (yeast) | coenzyme q | 1.0 | the voltage gradient across the mitochondrial membrane increases until a critical threshold is reached when electron transfer inside complex iii is blocked causing the electrons to back up to coenzyme q. the electron donated to molecular oxygen then generates superoxide. |
| 4141 | GAPDH | glyceraldehyde-3-phosphate dehydrogenase | glyceraldehyde 3 phosphate dehydrogenase | 1.0 | remise these free radicals induce deoxyribonucleic acid dna strand breaks to activate poly adenosine diphosphate ribose polymerase which modifies and reduces the activity of the key glycolytic enzyme glyceraldehyde 3 phosphate dehydrogenase gapdh . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | fig. 1 nadph oxidase implicated in the pathogenesis of diabetic complications. |
| 9393 | PRKCA | protein kinase C, alpha | protein kinase c | 1.0 | dag diacylglycerol pkc protein kinase c ages advanced glycation end products rage the receptor for ages ros reactive oxygen species. |
| 381 | AKR1B1 | aldo-keto reductase family 1, member B1 (aldose reductase) | aldose reductase | 1.0 | asterisk the rate limiting enzyme in the polyol pathway aldose reductase is upregulated under oxidative stress [ 129 130 ] whatever the source of superoxide it has become apparent in recent years that oxidative stress is an important element initiating diabetic macrovascu |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | on the other hand a different line of investigation demonstrated that nadph oxidase is the primary source of superoxide associated with diabetic vasculopathy. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in a prominent clinical study with the use of saphenous veins from patients undergoing coronary artery bypass surgery diabetes was shown to associate with increased vascular nadph oxidase activity and impaired nitric oxide no mediated endothelial dysfunction [ 10 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the subsequent study revealed that both the activity and the levels of nadph oxidase subunits were significantly increased in veins and arteries of type 2 diabetic patients. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | as increased superoxide production in diabetes was abrogated by an inhibitor of pkc chelerythrine [ 11 ] a primary role of nadph oxidase mediated by pkc signaling was suggested in the pathogenesis of endothelial dysfunction and ensuing vascular complications in human diabetes. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | nadph oxidase is therefore positioned downstream of pkc fig 1 . |
| 8800 | PDGFB | platelet-derived growth factor beta polypeptide (simian sarcoma viral (v-sis) oncogene homolog) | platelet derived growth factor | 1.0 | as various factors associated with diabetic conditions including angiotensin ii ang ii aldosterone endothelin 1 platelet derived growth factor pdgf tgf _amp_#946; and tumor necrosis factor _amp_#945; tnf _amp_#945; enhance the expression and activity of nadph oxidase the involvement of this oxidase was further endorsed in the pathogenesis o |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tumor necrosis factor | 1.0 | as various factors associated with diabetic conditions including angiotensin ii ang ii aldosterone endothelin 1 platelet derived growth factor pdgf tgf _amp_#946; and tumor necrosis factor _amp_#945; tnf _amp_#945; enhance the expression and activity of nadph oxidase the involvement of this oxidase was further endorsed in the pathogenesis of diabetic complications [ 12 _amp_#8211; 14 ] |
| 3176 | EDN1 | endothelin 1 | endothelin 1 | 1.0 | as various factors associated with diabetic conditions including angiotensin ii ang ii aldosterone endothelin 1 platelet derived growth factor pdgf tgf _amp_#946; and tumor necrosis factor _amp_#945; tnf _amp_#945; enhance the expression and activity of nadph oxidase the involvement of this oxidase was further |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | as various factors associated with diabetic conditions including angiotensin ii ang ii aldosterone endothelin 1 platelet derived growth factor pdgf tgf _amp_#946; and tumor necrosis factor _amp_#945; tnf _amp_#945; enhance the expression and activity of nadph oxidase the involvement of |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | including angiotensin ii ang ii aldosterone endothelin 1 platelet derived growth factor pdgf tgf _amp_#946; and tumor necrosis factor _amp_#945; tnf _amp_#945; enhance the expression and activity of nadph oxidase the involvement of this oxidase was further endorsed in the pathogenesis of diabetic complications [ 12 _amp_#8211; 14 ]. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | angiotensin ii | 1.0 | as various factors associated with diabetic conditions including angiotensin ii ang ii aldosterone endothelin 1 platelet derived growth factor pdgf tgf _amp_#946; and tumor necrosis factor _amp_#945; tnf _amp_#945; enhance the expression and activity of nadph oxidase the involve |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | nadph oxidase was first characterized in phagocytes where it plays an essential role in host defense. |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 phox | 1.0 | the classic phagocyte oxidase is a multicomponent enzyme consisting of the membrane bound catalytic subunit gp91 phox nox2 and p22 phox which associate with regulatory cytosolic subunits p47 phox p67 phox p40 phox and rac during the process of enzyme activation. |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | the classic phagocyte oxidase is a multicomponent enzyme consisting of the membrane bound catalytic subunit gp91 phox nox2 and p22 phox which associate with regulatory cytosolic subunits p47 phox p67 phox p40 phox and rac during the process of enzyme activation. |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 phox | 1.0 | the classic phagocyte oxidase is a multicomponent enzyme consisting of the membrane bound catalytic subunit gp91 phox nox2 and p22 phox which associate with regulatory cytosolic subunits p47 phox p67 phox p40 phox and rac during the process of enzyme activation. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | herein we explore the potential mechanisms by which nadph oxidase contributes to the initiation and progress of diabetic complications. |
| 6081 | INS | insulin | insulin | 1.0 | the involvement of oxidative stress in the development of atherosclerosis has been suggested by the fact that numerous risk factors of atherosclerosis including hyperglycemia insulin resistance hypertension hyperlipidemia and obesity are closely associated with generation of ros. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | extensive reports point out the relevance of ros derived from nadph oxidase to the atherosclerotic lesion. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | while oxidized low density lipoprotein strongly stimulates ros production by nadph oxidase in endothelial cells [ 17 ] activation of the receptor for ages rage by ages also induces ros production via nadph oxidase in the vasculature [ 18 ]. |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 phox | 1.0 | in fact a diet induced primate model of atherosclerosis displayed an increased ros level accompanied by the upregulation of p22 phox and p47 phox in the affected arteries [ 20 ]. |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 phox | 1.0 | abundant expression of nox2 is documented in human atherosclerotic plaques [ 21 ] and expression levels of nox2 and p22 phox in human coronary arteries correlated with the severity of atherosclerosis [ 22 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | as recent reports propose that antioxidative and anti inflammatory effects of statins are attributed to the inhibition of nadph oxidase activity [ 23 ] the therapeutic efficacy of statins further supports a potential role of this oxidase in the development of atherosclerosis. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in cultured bovine pericytes palmitate the major saturated ffa in plasma induces apoptosis and palmitate induced apoptosis was associated with increased oxidative stress derived from nadph oxidase [ 26 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the molecular interactions between palmitate and nadph oxidase remain to be clarified. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | however the fact that elevated ffa levels are found in type 2 diabetic patients and are associated with obesity and the metabolic syndrome further endorse the role of nadph oxidase in the pathogenesis of diabetic vascular complications. |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 phox | 1.0 | expression of the catalytic subunit of nadph oxidase nox1 along with other membrane and cytosolic subunits p22 phox p47 phox and p67 phox was documented in a cultured cell line established from rat adipose tissue microvasculature. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | expression of the catalytic subunit of nadph oxidase nox1 along with other membrane and cytosolic subunits p22 phox p47 phox and p67 phox was documented in a cultured cell line established from rat adipose tissue microvasculature. |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 phox | 1.0 | expression of the catalytic subunit of nadph oxidase nox1 along with other membrane and cytosolic subunits p22 phox p47 phox and p67 phox was documented in a cultured cell line established from rat adipose tissue microvasculature. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | these cells express morphological biochemical and functional similarities to pericytes isolated from the retina and upregulate p22 phox when exposed to high glucose or ang ii [ 27 ]. |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 phox | 1.0 | these cells express morphological biochemical and functional similarities to pericytes isolated from the retina and upregulate p22 phox when exposed to high glucose or ang ii [ 27 ]. |
| 6204 | JUN | jun oncogene | c jun | 1.0 | the activation of pkc _amp_#948; and increased c jun n terminal kinase jnk phosphorylation was demonstrated in cells under cyclic stretch. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | immunoprecipitation and immunoblot analyses showed rapid association of pkc _amp_#948; with p47 phox in these cells and inhibitors of nadph oxidase diphenylene iodonium dpi and apocynin suppressed the generation of ros. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | these findings suggest that nadph oxidase in retinal pericytes accelerates early diabetic retinopathy in the presence of hypertension. |
| 12680 | VEGFA | vascular endothelial growth factor A | vegf a | 1.0 | ages have been shown to elicit an angiogenic response by production of vegf a potent growth factor that stimulates proliferation migration and tube formation of endothelial cells. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | these findings corroborated the finding that ros derived from nadph oxidase modulate vegf induced angiogenesis [ 30 ]. |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | chronic granulomatous disease | 1.0 | in this context it should be pointed out that patients with chronic granulomatous disease cgd frequently have chorioretinal lesions. |
| 30802 | PNPLA2 | patatin-like phospholipase domain containing 2 | pigment epithelium derived factor | 1.0 | pigment epithelium derived factor pedf a glycoprotein that belongs to the superfamily of serine protease inhibitors represses the growth and migration of cultured endothelial cells. |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 phox | 1.0 | in the eye of age treated rats mrna levels of both p22 phox and nox2 were significantly elevated while pedf treatments suppressed this upregulation. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | it remains to be clarified however how pedf affects the expression of nadph oxidase subunits in the eye. |
| 399 | ALB | albumin | albumin | 1.0 | these factors and cytokines provoke the accumulation of ecm and hemodynamic alterations leading to hypertrophy of mesangial cells mcs increased intraglomerular pressure and ensuing albumin leakage. |
| 6081 | INS | insulin | insulin | 1.0 | ros are proposed to link various adverse events taking place under diabetic conditions such as lipid peroxidation adhesion molecule expression associated with cellular infiltration and insulin resistance [ 36 ]. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | these processes are mediated respectively by transforming growth factor _amp_#946; tgf _amp_#946; plasminogen activator inhibitor 1 pai 1 p53 caspase 3 monocyte chemoattractant protein 1 mcp 1 osteopontin and nitric oxide no |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | monocyte chemoattractant protein 1 | 1.0 | these processes are mediated respectively by transforming growth factor _amp_#946; tgf _amp_#946; plasminogen activator inhibitor 1 pai 1 p53 caspase 3 monocyte chemoattractant protein 1 mcp 1 osteopontin and nitric oxide no |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | plasminogen activator inhibitor | 1.0 | these processes are mediated respectively by transforming growth factor _amp_#946; tgf _amp_#946; plasminogen activator inhibitor 1 pai 1 p53 caspase 3 monocyte chemoattractant protein 1 mcp 1 osteopontin and nitric oxide no |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | plasminogen activator inhibitor 1 | 1.0 | these processes are mediated respectively by transforming growth factor _amp_#946; tgf _amp_#946; plasminogen activator inhibitor 1 pai 1 p53 caspase 3 monocyte chemoattractant protein 1 mcp 1 osteopontin and nitric oxide no |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | osteopontin | 1.0 | these processes are mediated respectively by transforming growth factor _amp_#946; tgf _amp_#946; plasminogen activator inhibitor 1 pai 1 p53 caspase 3 monocyte chemoattractant protein 1 mcp 1 osteopontin and nitric oxide no |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | mcp 1 | 1.0 | these processes are mediated respectively by transforming growth factor _amp_#946; tgf _amp_#946; plasminogen activator inhibitor 1 pai 1 p53 caspase 3 monocyte chemoattractant protein 1 mcp 1 osteopontin and nitric oxide no |
| 11765 | TGFA | transforming growth factor, alpha | transforming growth factor | 1.0 | these processes are mediated respectively by transforming growth factor _amp_#946; tgf _amp_#946; plasminogen activator inhibitor 1 pai 1 p53 caspase 3 monocyte chemoattractant protein 1 mcp 1 osteopontin and nitric oxide no |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | pai 1 | 1.0 | these processes are mediated respectively by transforming growth factor _amp_#946; tgf _amp_#946; plasminogen activator inhibitor 1 pai 1 p53 caspase 3 monocyte chemoattractant protein 1 mcp 1 osteopontin and nitric oxide no |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | monocyte chemoattractant protein 1 | 1.0 | the growth factors and cytokines elevated under hyperglycemia tgf _amp_#946; pdgf tnf _amp_#945; pai 1 and monocyte chemoattractant protein 1 mcp 1 induce mesangial expansion by accumulating ecm components in the glomerular mesangium. |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | mcp 1 | 1.0 | the growth factors and cytokines elevated under hyperglycemia tgf _amp_#946; pdgf tnf _amp_#945; pai 1 and monocyte chemoattractant protein 1 mcp 1 induce mesangial expansion by accumulating ecm components in the glomerular mesangium. |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | pai 1 | 1.0 | the growth factors and cytokines elevated under hyperglycemia tgf _amp_#946; pdgf tnf _amp_#945; pai 1 and monocyte chemoattractant protein 1 mcp 1 induce mesangial expansion by accumulating ecm components in the glomerular mesangium. |
| 1516 | CAT | catalase | catalase | 1.0 | pretreatment with catalase or antioxidants prevents high glucose or h 2 o 2 induced expression of tgf _amp_#946;1 and reduces ecm proteins in mcs [ 43 _amp_#8211; 45 ]. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | along with hemodynamic effects ang ii stimulates the synthesis of ecm components by acting on mcs. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | while a clear link between ang ii induced ros production and hypertrophy of mcs was documented [ 52 ] experimental studies in vivo and in vitro demonstrated that the production of mesangial ecm components is augmented by ang ii via t |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | induced ros production and hypertrophy of mcs was documented [ 52 ] experimental studies in vivo and in vitro demonstrated that the production of mesangial ecm components is augmented by ang ii via the upregulation of tgf _amp_#946; [ 53 ]. |
| 9071 | PLG | plasminogen | plasminogen | 1.0 | another system is the plasminogen activator_amp_#8211;plasmin_amp_#8211;pai system. |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | pai 1 | 1.0 | these systems correlate with each other [ 55 56 ] given that increased pai 1 in renal diseases prevents the activation of mmps and the degradation of ecm by reducing plasmin. |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | pai 1 | 1.0 | previous studies confirmed that mmps timp and pai 1 are regulated by high glucose. |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | pai 1 | 1.0 | of studies found that antioxidants rescued reduced plasmin activity that regulates mmps in mcs exposed to high glucose and anti tgf _amp_#946; antibody inhibited both high glucose and h 2 o 2 induced pai 1 upregulation [ 58 59 ]. |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | pai 1 | 1.0 | these findings suggest that ros mediate both high glucose and tgf _amp_#946;1 induced pai 1 expression and qualify ros as intracellular messengers that play a crucial role in the accumulation of ecm and ensuing renal hypertrophy glomerulosclerosis and fibrosis. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | in transgenic mice overexpressing catalase in their proximal tubular cells ros production and expressions of proapoptotic genes such as p53 bax and caspase 3 are attenuated along with reduced proximal tubular cell apoptosis at 2 weeks after stz induced hyperglycemia [ 63 ]. |
| 1516 | CAT | catalase | catalase | 1.0 | in transgenic mice overexpressing catalase in their proximal tubular cells ros production and expressions of proapoptotic genes such as p53 bax and caspase 3 are attenuated along with reduced proximal tubular cell apoptosis at 2 weeks after s |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | increased extracellular glucose rapidly stimulates the generation of ros which leads to activation of proapoptotic caspase 3 and apoptosis in conditionally immortalized cultured podocytes [ 65 ]. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | besides glucose induced generation of ros ang ii induced generation of ros is also documented to induce apoptosis in mcs [ 66 ]. |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | osteopontin | 1.0 | ros and inflammation similar to tgf _amp_#946;1 and pai 1 mentioned above ros upregulate various chemokines including mcp 1 osteopontin migration inhibitory factor and monocyte colony stimulating factor which amplify glomerular damage and accelerate the development of glomerulosclerosis. |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | mcp 1 | 1.0 | ros and inflammation similar to tgf _amp_#946;1 and pai 1 mentioned above ros upregulate various chemokines including mcp 1 osteopontin migration inhibitory factor and monocyte colony stimulating factor which amplify glomerular damage and accelerate the development of glomerulosclerosis. |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | pai 1 | 1.0 | ros and inflammation similar to tgf _amp_#946;1 and pai 1 mentioned above ros upregulate various chemokines including mcp 1 osteopontin migration inhibitory factor and monocyte colony stimulating factor which amplify glomerular damage and accelerate the dev |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | mcp 1 | 1.0 | mcp 1 recruits monocytes and lymphocytes and induces glomerular and interstitial inflammation in response to renal injury. |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | mcp 1 | 1.0 | in cultured mcs and podocytes ros have been shown to mediate the expression of mcp 1 induced by high glucose tnf _amp_#945; tgf _amp_#946; and ages through the activation of nuclear factor kappab nf _amp_#954;b [ 68 _amp_#8211; 71 ]. |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | osteopontin | 1.0 | similarly the induction of osteopontin which enhances leukocyte infiltration during renal inflammation and fibrosis is mediated by ros production [ 72 ]. |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | interleukin 6 | 1.0 | since increased generation of ros by interleukin 6 and interleukin 1_amp_#946; is also demonstrated [ 73 ] ros signaling affects the inflammatory response involved in the development of diabetic nephropathy. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the expression of nadph oxidase subtype in the kidney |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | nadph oxidase has been postulated as a main source of ros production in the kidney [ 79 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | we now summarize the localization of each component of nadph oxidase classified by membrane and cytosolic subunits tables 1 and 2 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the localization of nadph oxidase subunits in the kidney was also assessed by gill and wilcox [ 80 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | table 1 localization of membrane components of nadph oxidase in renal tissue and cultured cells |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | table 2 localization of cytosolic components of nadph oxidase in renal tissue and cultured cells |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | these nox isoforms are upregulated by multiple factors including ang ii ages and a high salt diet associated with the metabolic syndrome table 3 fig 3 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | fig. 3 nadph oxidase and signaling pathways involved in ecm accumulation and fibrotic changes in diabetic kidney. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | high glucose hg ang ii and ages elicit activation of pkc and nadph oxidase. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | high glucose hg ang ii and ages elicit activation of pkc and nadph oxidase. |
| 3796 | FOS | v-fos FBJ murine osteosarcoma viral oncogene homolog | ap 1 | 1.0 | ros derived from nadph oxidase turn on signal transduction cascades and two master transcription factors ap 1 and nf _amp_#954;b leading to the up regulation of tgf _amp_#946; pai 1 and mcp 1 involved in the ecm turnover and the development of renal fibrosis. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | ros derived from nadph oxidase turn on signal transduction cascades and two master transcription factors ap 1 and nf _amp_#954;b leading to the up regulation of tgf _amp_#946; pai 1 and mcp 1 involved in the ecm turnover and the d |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | mcp 1 | 1.0 | ros derived from nadph oxidase turn on signal transduction cascades and two master transcription factors ap 1 and nf _amp_#954;b leading to the up regulation of tgf _amp_#946; pai 1 and mcp 1 involved in the ecm turnover and the development of renal fibrosis. |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | pai 1 | 1.0 | ros derived from nadph oxidase turn on signal transduction cascades and two master transcription factors ap 1 and nf _amp_#954;b leading to the up regulation of tgf _amp_#946; pai 1 and mcp 1 involved in the ecm turnover and the development of renal fibrosis. |
| 3796 | FOS | v-fos FBJ murine osteosarcoma viral oncogene homolog | ap 1 | 1.0 | erk1/2 extracellular signal regulated kinases 1 and 2 akt/pkb akt/protein kinase b ap 1 activated protein 1 nf _amp_#954;b nuclear factor kappab mmp matrix metalloproteinases |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | protein kinase b | 1.0 | erk1/2 extracellular signal regulated kinases 1 and 2 akt/pkb akt/protein kinase b ap 1 activated protein 1 nf _amp_#954;b nuclear factor kappab mmp matrix metalloproteinases |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | table 3 upregulation of nadph oxidase components in renal tissue of various animal models |
| 6554 | LEPR | leptin receptor | leptin receptor | 1.0 | stz streptozotocin induced diabetic model duration of hyperglycemia ; db/db leptin receptor deficient type 2 diabetic model ang ii angiotensin ii induced hypertension model shr spontaneously hypertensive rat ds dahl salt sensitive rat m mouse r rat |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | stz streptozotocin induced diabetic model duration of hyperglycemia ; db/db leptin receptor deficient type 2 diabetic model ang ii angiotensin ii induced hypertension model shr spontaneously hypertensive rat ds dahl salt sensitive rat m mouse r rat |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | angiotensin ii | 1.0 | stz streptozotocin induced diabetic model duration of hyperglycemia ; db/db leptin receptor deficient type 2 diabetic model ang ii angiotensin ii induced hypertension model shr spontaneously hypertensive rat ds dahl salt sensitive rat m mouse r rat |
| 6081 | INS | insulin | insulin | 1.0 | the increased level of nox4 is recovered by insulin treatment [ 84 ]. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | the expression of nox4 is verified in mcs and nox4 derived ros was documented to mediate ang ii induced signaling and protein synthesis by the activation of extracellular signal regulated kinases 1 and 2 erk1/erk2 [ 85 86 ]. |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 phox | 1.0 | the study showed that the nox1 gene is located in the linkage regions along with p22 phox and nox3 genes. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | although ros derived from nox1 have been implicated in ang ii mediated hypertension [ 90 _amp_#8211; 92 ] whether nox1 in the kidney takes part in the development of hypertension has not been fully defined. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | chabrashvili et al. demonstrated that ang ii infused mice promote oxidative stress in the renal cortex via increased mrna expression of nox1 and p22 phox but not of nox4 [ 93 ]. |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 phox | 1.0 | chabrashvili et al. demonstrated that ang ii infused mice promote oxidative stress in the renal cortex via increased mrna expression of nox1 and p22 phox but not of nox4 [ 93 ]. |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 phox | 1.0 | in dahl salt sensitive hypertensive rats which exhibit a higher ratio of urinary protein excretion and cortical collagen content an increased renal cortical expression of nox1 and p22 phox accompanied by the activation of erk1/erk2 was demonstrated [ 94 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | more recently nox1 containing nadph oxidase was suggested in the modulation of renal oxidative stress and redox dependent signaling of c src p38 mitogen activated protein kinase mapk jnk and focal adhesion kinase [ 95 ]. |
| 11283 | SRC | v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) | c src | 1.0 | more recently nox1 containing nadph oxidase was suggested in the modulation of renal oxidative stress and redox dependent signaling of c src p38 mitogen activated protein kinase mapk jnk and focal adhesion kinase [ 95 ]. |
| 6876 | MAPK14 | mitogen-activated protein kinase 14 | p38 mitogen activated protein kinase | 1.0 | more recently nox1 containing nadph oxidase was suggested in the modulation of renal oxidative stress and redox dependent signaling of c src p38 mitogen activated protein kinase mapk jnk and focal adhesion kinase [ 95 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | similarly increased nadph oxidase activity and increased expressions of p47 phox nox2 and nox4 mrna levels in the renal cortex were observed in stz induced diabetic mice at 8 weeks [ 97 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in these animal models the enhancement of oxidative stress is attributed to an increased renal superoxide generation by nadph oxidase. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | pathological mechanisms mediated by nadph oxidase in diabetic nephropathy while ros derived from nadph oxidase have been implicated in the pathogenesis of diabetic nephropathy the molecular mechanisms mediated by nadph oxidase are not fully elucidated. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | have been implicated in the pathogenesis of diabetic nephropathy the molecular mechanisms mediated by nadph oxidase are not fully elucidated. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | recent studies revealed the role of nadph oxidase as a signal transducer in ecm accumulation as well as in apoptotic cell death associated with the development of diabetic complications. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the cross talk of nadph oxidase with pkc and mapk cascades has also been extensively studied. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | ecm accumulation and nadph oxidase |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | as pkc is implicated in the phosphorylation of p47 phox that organizes the translocation of other cytosolic subunits to the membrane components of nadph oxidase an event required for oxidase activation increased pkc activity under high glucose leads to the activation of the oxidase. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | this highlights a close relationship between increased pkc activity and activation of nadph oxidase demonstrated in diabetes [ 11 ]. |
| 399 | ALB | albumin | albumin | 1.0 | treatment with a specific inhibitor of pkc _amp_#946; ly333531 or ruboxistaurin indeed recovered reduced gfr and increased albumin excretion to improve renal dysfunctions observed in a diabetic model [ 104 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in accord with these findings pkc _amp_#946; is shown to activate nadph oxidase in hl60 cells differentiated to a neutrophil like phenotype as well as in primary neutrophils [ 105 106 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | pkc _amp_#946; but also the _amp_#945; _amp_#948; and _amp_#950; isoforms expressed in human neutrophils can individually phosphorylate p47 phox and induce its translocation and ensuing activation of nadph oxidase [ 107 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | aside from these in vitro findings the molecular link between pkc _amp_#946; and nadph oxidase is further verified by a study using pkc _amp_#946; null mice. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in these mice the reduction in nadph oxidase activity accompanied by decreased expressions of p47 phox nox2 and nox4 mrnas is demonstrated in the renal cortex suggesting that a lack of pkc _amp_#946; can protect against increased expressions of |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | activity accompanied by decreased expressions of p47 phox nox2 and nox4 mrnas is demonstrated in the renal cortex suggesting that a lack of pkc _amp_#946; can protect against increased expressions of nadph oxidase subunits under diabetic conditions [ 97 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | these data clearly illustrate the direct link between pkc and nadph oxidase pkc being the upstream node of nadph oxidase to regulate the enzyme activity. |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 phox | 1.0 | another study showed that a conventional pkc pkc _amp_#945; and pkc _amp_#946; inhibitor g6976 suppresses increased expressions of p22 phox p47 phox and collagen iv along with reduced ros production in mcs under high glucose condition [ 108 ]. |
| 2202 | COL4A1 | collagen, type IV, alpha 1 | collagen iv | 1.0 | another study showed that a conventional pkc pkc _amp_#945; and pkc _amp_#946; inhibitor g6976 suppresses increased expressions of p22 phox p47 phox and collagen iv along with reduced ros production in mcs under high glucose condition [ 108 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in stz induced diabetic rats and in mcs treated with ages the activation of nadph oxidase via the phosphorylation of pkc _amp_#945; takes place downstream of the ages and rage interaction [ 109 ]. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | ang ii acts as an important factor that initiates mesangial ecm accumulation. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | in addition to its hemodynamic effects growth stimulating signals driven by ang ii promote mc hypertrophy and ecm production. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | ang ii elicits nadph oxidase dependent superoxide production in mcs and increases protein content which is prevented by dpi or pkc inhibitors [ 52 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | ang ii elicits nadph oxidase dependent superoxide production in mcs and increases protein content which is prevented by dpi or pkc inhibitors [ 52 ]. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | the activation of nadph oxidase by ang ii is therefore suggested to be a pkc dependent process in mcs. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the activation of nadph oxidase by ang ii is therefore suggested to be a pkc dependent process in mcs. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | subsequently nox isoforms activated by ang ii in the kidney have been explored. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | nox4 is currently recognized as a target of ang ii since antisense oligonucleotides against nox4 decrease ang ii induced ros production activation of akt/pkb and erk1/2 and protein synthesis in mcs [ 85 86 ]. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | in contrast to these findings there is a study demonstrating that ang ii infusion into rats augments oxidative stress and upregulates the renal cortical expression of nox1 and p22 phox mrnas but reduces the expression of nox4 via ang ii type 1 receptor at 1 [ 93 ]. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | infusion into rats augments oxidative stress and upregulates the renal cortical expression of nox1 and p22 phox mrnas but reduces the expression of nox4 via ang ii type 1 receptor at 1 [ 93 ]. |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 phox | 1.0 | in contrast to these findings there is a study demonstrating that ang ii infusion into rats augments oxidative stress and upregulates the renal cortical expression of nox1 and p22 phox mrnas but reduces the expression of nox4 via ang ii type 1 receptor at 1 [ 93 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | whichever nox isoform is involved these results suggest that pkc plays a key role in diabetes induced nadph oxidase activation in the kidney. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | r pkc isoforms are implicated in retinal pericytes in vivo and in vitro studies in the kidney illustrate the involvement of pkc _amp_#945; and _amp_#946; isoform in increased superoxide production by nadph oxidase. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | ros generated by nadph oxidase under high glucose act as second messengers to activate the signal transduction cascade via p38 mapk and erk. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | an antioxidant n acetylcysteine and an inhibitor of nadph oxidase dpi indeed inhibit the activation of p38 mapk in mcs [ 110 ]. |
| 3796 | FOS | v-fos FBJ murine osteosarcoma viral oncogene homolog | ap 1 | 1.0 | further downstream of the signal transduction cascade ros activate two master transcription factors nf _amp_#954;b and activated protein 1 ap 1 leading to the upregulation of respective target genes [ 42 ]. |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | mcp 1 | 1.0 | among these genes are fibrotic cytokines such as mcp 1 tgf _amp_#946; and pai 1 as well as ecm proteins including fibronectin and collagens. |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | pai 1 | 1.0 | among these genes are fibrotic cytokines such as mcp 1 tgf _amp_#946; and pai 1 as well as ecm proteins including fibronectin and collagens. |
| 3796 | FOS | v-fos FBJ murine osteosarcoma viral oncogene homolog | ap 1 | 1.0 | previous reports show that nf _amp_#954;b regulates mcp 1 expression [ 69 ] while ap 1 mediates a high glucose induced increase in tgf _amp_#946;1 gene promoter activity [ 111 ]. |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | mcp 1 | 1.0 | previous reports show that nf _amp_#954;b regulates mcp 1 expression [ 69 ] while ap 1 mediates a high glucose induced increase in tgf _amp_#946;1 gene promoter activity [ 111 ]. |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | pai 1 | 1.0 | in cultured mcs and in diabetic glomeruli the involvement of ros was recognized in high glucose and tgf _amp_#946;1 induced upregulation of pai 1 expression. |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | pai 1 | 1.0 | both high glucose and tgf _amp_#946;1 induce cellular ros while ros mediate both high glucose and tgf _amp_#946;1 induced pai 1 expression. |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | pai 1 | 1.0 | increased pai 1 then attenuates plasmin and mmp activity to perturb ecm degradation. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | accordingly ros derived from nadph oxidase activate the signal transduction cascade and transcription factors to incite expression of genes involved in the regulation of balance between the synthesis and degradation of ecm fig 3 . |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | protein kinase b | 1.0 | in stz induced diabetic rats the activation of akt/protein kinase b and erk1/2 was demonstrated downstream of nox4 containing nadph oxidase. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in stz induced diabetic rats the activation of akt/protein kinase b and erk1/2 was demonstrated downstream of nox4 containing nadph oxidase. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | similar to ang ii induced signaling nox4 is again suggested as an upstream activator of erk1/2 and akt/pkb both critical for cell growth and hypertrophy under hyperglycemia. |
| 399 | ALB | albumin | albumin | 1.0 | apoptosis signaling and nadph oxidase while the first manifestation of nephropathy in diabetic patients is increased urinary albumin excretion very little is known about the cellular events that precede the onset of clinical albuminuria. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | apoptosis signaling and nadph oxidase while the first manifestation of nephropathy in diabetic patients is increased urinary albumin excretion very little is known about the cellular events that precede the onset of clinical albuminuria. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | extracellular glucose elicits generation of superoxide by nadph oxidase and leads to the activation of proapoptotic p38 mapk and caspase 3 in cultured podocytes. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | extracellular glucose elicits generation of superoxide by nadph oxidase and leads to the activation of proapoptotic p38 mapk and caspase 3 in cultured podocytes. |
| 399 | ALB | albumin | albumin | 1.0 | the systemic administration of a nadph oxidase inhibitor apocynin prevented podocyte apoptosis and ameliorated urinary albumin excretion in diabetic mice [ 65 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the systemic administration of a nadph oxidase inhibitor apocynin prevented podocyte apoptosis and ameliorated urinary albumin excretion in diabetic mice [ 65 ]. |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 phox | 1.0 | in cultured murine podocytes the expression of nox4 and p22 phox mrna was confirmed whereas the expression of nox2 was documented in human cultured podocytes [ 113 ]. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | in proximal tubules isolated from transgenic mice overexpressing catalase in a kidney specific manner the induction of proapoptotic genes p53 bax and caspase 3 under stz induced diabetes was attenuated [ 63 ]. |
| 1516 | CAT | catalase | catalase | 1.0 | in proximal tubules isolated from transgenic mice overexpressing catalase in a kidney specific manner the induction of proapoptotic genes p53 bax and caspase 3 under stz induced diabetes was attenuated [ 63 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | a therapeutic target for diabetic nephropathy from the information available so far ros derived from nadph oxidase act as a potent causal factor that initiates and accelerates the development of diabetic renal complication. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | nadph oxidase hence becomes a potential target for pharmacological intervention of diabetic nephropathy. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | at present the blockade of ras with angiotensin converting enzyme ace inhibitors and ang ii receptor blockers arbs is the most successful therapeutic approach to prevent or improve the renal disorders in diabetic patients [ 115 116 ]. |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | angiotensin converting enzyme | 1.0 | at present the blockade of ras with angiotensin converting enzyme ace inhibitors and ang ii receptor blockers arbs is the most successful therapeutic approach to prevent or improve the renal disorders in diabetic patients [ 115 116 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | since both ace inhibitors and arb suppress renal ros production p47 phox expression and microalbuminuria in stz induced diabetic rats [ 117 ] the inhibition of nadph oxidase that blocks the signaling pathway downstream of ras may offer a novel approach to delay the onset of renal dysfunction. |
| 5006 | HMGCR | 3-hydroxy-3-methylglutaryl-Coenzyme A reductase | 3 hydroxy 3 methylglutaryl coenzyme a reductase | 1.0 | recently several reports have demonstrated beneficial effects of inhibitors of 3 hydroxy 3 methylglutaryl coenzyme a reductase statins on diabetic nephropathy. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | besides their cholesterol lowering effect statins inhibit rac acylation thus perturbing the translocation of rac to the membrane fraction required for activation of nadph oxidase. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | high glucose or ang ii induced activation of mapk in mcs was also completely blocked by pitavastatin as well as by dpi suggesting that the effects of pitavastatin on diabetic nephropathy work through the inhibition of nadp |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | g ii induced activation of mapk in mcs was also completely blocked by pitavastatin as well as by dpi suggesting that the effects of pitavastatin on diabetic nephropathy work through the inhibition of nadph oxidase [ 118 ]. |
| 11416 | STN | statin | statin | 1.0 | all of these findings provide evidence for the involvement of the nadph oxidase mediated mechanisms in the usefulness of statin therapy. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | all of these findings provide evidence for the involvement of the nadph oxidase mediated mechanisms in the usefulness of statin therapy. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the activation of rage leads to the intracellular generation of ros and nadph oxidase is suggested as a source of ros produced by ages/rage interaction [ 18 ]. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | in drg neurons exposed to a rage ligand or hyperglycemia the activation of rage leads to an increased generation of ros by nadph oxidase within 1 h while the activation of caspase 3 and degradation of nuclear dna were observed after 6 h in more than 70% of neurons. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in drg neurons exposed to a rage ligand or hyperglycemia the activation of rage leads to an increased generation of ros by nadph oxidase within 1 h while the activation of caspase 3 and degradation of nuclear dna were observed after 6 h in more than 70% of neurons. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | accordingly the activation of nadph oxidase in drg neurons elicits subsequent oxidative stress and neuronal injury downstream of the ages/rage interaction [ 119 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | nadph oxidase and the mitochondrial electron transport chain take part in the increased superoxide generation in the sciatic nerve of diabetic rats [ 120 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | similar to larger vessels reduced no availability due to increased superoxide formation by nadph oxidase leads to the impairment of the endothelium dependent vasodilation in arterioles feeding nervous structures under diabetic conditions. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | conclusion increased nadph oxidase activity in tissues vulnerable to hyperglycemia takes place downstream of the pkc and ages two of the primary mechanisms involved in the pathogenesis of diabetic complications. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | among these agents pkc _amp_#946; inhibitors and aldosterone blockers indirectly suppress nadph oxidase activity while an sod mimetic tempol an antioxidant _amp_#945; lipoic acid and apocynin directly abrogate nadph oxidase activity. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | activity while an sod mimetic tempol an antioxidant _amp_#945; lipoic acid and apocynin directly abrogate nadph oxidase activity. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | thus compounds that suppress nadph oxidase activity may offer therapeutic benefits to ameliorate diabetic complications highlighting the significance of nadph oxidase as a new therapeutic target. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | it remains to be determined however whether the attenuation of isoform specific nadph oxidase activity improves the incidence and progression of long term complications in diabetic patients. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | further investigation using isoform specific knockout mice may aid in understanding the role of nadph oxidase in diabetic complications. |