| First Author | Nayak BK | Year | 2016 |
| Journal | Diabetes | Volume | 65 |
| Issue | 5 | Pages | 1387-97 |
| PubMed ID | 26908870 | Mgi Jnum | J:246631 |
| Mgi Id | MGI:5922732 | Doi | 10.2337/db15-0519 |
| Citation | Nayak BK, et al. (2016) HIF-1 Mediates Renal Fibrosis in OVE26 Type 1 Diabetic Mice. Diabetes 65(5):1387-97 |
| abstractText | Hypoxia-inducible factor (HIF)-1 mediates hypoxia- and chronic kidney disease-induced fibrotic events. Here, we assessed whether HIF-1 blockade attenuates the manifestations of diabetic nephropathy in a type 1 diabetic animal model, OVE26. YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole], an HIF-1 inhibitor, reduced whole kidney glomerular hypertrophy, mesangial matrix expansion, extracellular matrix accumulation, and urinary albumin excretion as well as NOX4 protein expression and NADPH-dependent reactive oxygen species production, while blood glucose levels remained unchanged. The role of NOX oxidases in HIF-1-mediated extracellular matrix accumulation was explored in vitro using glomerular mesangial cells. Through a series of genetic silencing and adenoviral overexpression studies, we have defined GLUT1 as a critical downstream target of HIF-1alpha mediating high glucose-induced matrix expression through the NADPH oxidase isoform, NOX4. Together, our data suggest that pharmacological inhibition of HIF-1 may improve clinical manifestations of diabetic nephropathy. |
