| First Author | Iguchi M | Year | 2008 |
| Journal | Nephron Exp Nephrol | Volume | 110 |
| Issue | 3 | Pages | e82-90 |
| PubMed ID | 18957870 | Mgi Jnum | J:155367 |
| Mgi Id | MGI:4413550 | Doi | 10.1159/000166994 |
| Citation | Iguchi M, et al. (2008) Acute inactivation of the VHL gene contributes to protective effects of ischemic preconditioning in the mouse kidney. Nephron Exp Nephrol 110(3):e82-90 |
| abstractText | BACKGROUND/AIMS: The von Hippel-Lindau (VHL) protein functions as an E3 ubiquitin ligase, controlling the stability of hypoxia-inducible factor (HIF). Preinduction of HIF-1alpha before pathological insult activates a self-defense mechanism and suppresses further aggravation of organ or cellular injury by ischemia. We investigated whether acute inactivation of the VHL gene might play a role in the response of mice to ischemic renal injury. METHODS: We generated tamoxifen-inducible conditional VHL knockout (VHL-KO) mice to inactivate the VHL gene in an acute manner during renal ischemia-reperfusion injury (IRI) induced by bilateral clamping of kidney arteries. Renal IRI is characterized by renal dysfunction and tubular damage. RESULTS: After the procedure of IRI, blood urea nitrogen (BUN) and creatinine (CRN) levels in control mice were significantly higher (BUN, 138.10 +/- 13.03 mg/dl; CRN, 0.72 +/- 0.16 mg/dl) than in VHL-KO mice (BUN, 52.12 +/- 6.61 mg/dl; CRN, 0.24 +/- 0.04 mg/dl; BUN: p < 0.05; CRN: p < 0.05). Histologically, tubular injury scores were higher in control mice than in VHL-KO mice (p < 0.05). CONCLUSION: We suggest that the acute inactivation of the VHL gene contributes to protective effects of ischemic preconditioning in renal tubules of the mouse. |
