| First Author | Kimura K | Year | 2008 |
| Journal | Am J Physiol Renal Physiol | Volume | 295 |
| Issue | 4 | Pages | F1023-9 |
| PubMed ID | 18667485 | Mgi Jnum | J:153791 |
| Mgi Id | MGI:4366234 | Doi | 10.1152/ajprenal.90209.2008 |
| Citation | Kimura K, et al. (2008) Stable expression of HIF-1alpha in tubular epithelial cells promotes interstitial fibrosis. Am J Physiol Renal Physiol 295(4):F1023-9 |
| abstractText | Chronic hypoxia accelerates renal fibrosis. The chief mediator of the hypoxic response is hypoxia-inducible factor 1 (HIF-1) and its oxygen-sensitive component HIF-1alpha. HIF-1 regulates a wide variety of genes, some of which are closely associated with tissue fibrosis. To determine the specific role of HIF-1 in renal fibrosis, we generated a knockout mouse in which tubular epithelial expression of von Hippel-Lindau tumor suppressor (VHL), which acts as a ubiquitin ligase to promote proteolysis of HIF-1alpha, was targeted. We investigated the effect of VHL deletion (i.e., stable expression of HIF-1alpha) histologically and used the anti-HIF-1alpha agent [3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole] (YC-1) to test whether inhibition of HIF-1alpha could represent a novel approach to treating renal fibrosis. The area of renal fibrosis was significantly increased in a 5/6 renal ablation model of VHL-/- mice and in all VHL-/- mice at least 60 wk of age. Injection of YC-1 inhibited the progression of renal fibrosis in unilateral ureteral obstruction model mice. In conclusion, HIF-1alpha appears to be a critical contributor to the progression of renal fibrosis and could be a useful target for its treatment. |
