| First Author | Kapitsinou PP | Year | 2014 |
| Journal | J Clin Invest | Volume | 124 |
| Issue | 6 | Pages | 2396-409 |
| PubMed ID | 24789906 | Mgi Jnum | J:212930 |
| Mgi Id | MGI:5582545 | Doi | 10.1172/JCI69073 |
| Citation | Kapitsinou PP, et al. (2014) Endothelial HIF-2 mediates protection and recovery from ischemic kidney injury. J Clin Invest 124(6):2396-409 |
| abstractText | The hypoxia-inducible transcription factors HIF-1 and HIF-2 mediate key cellular adaptions to hypoxia and contribute to renal homeostasis and pathophysiology; however, little is known about the cell type-specific functions of HIF-1 and HIF-2 in response to ischemic kidney injury. Here, we used a genetic approach to specifically dissect the roles of endothelial HIF-1 and HIF-2 in murine models of hypoxic kidney injury induced by ischemia reperfusion or ureteral obstruction. In both models, inactivation of endothelial HIF increased injury-associated renal inflammation and fibrosis. Specifically, inactivation of endothelial HIF-2alpha, but not endothelial HIF-1alpha, resulted in increased expression of renal injury markers and inflammatory cell infiltration in the postischemic kidney, which was reversed by blockade of vascular cell adhesion molecule-1 (VCAM1) and very late antigen-4 (VLA4) using monoclonal antibodies. In contrast, pharmacologic or genetic activation of HIF via HIF prolyl-hydroxylase inhibition protected wild-type animals from ischemic kidney injury and inflammation; however, these same protective effects were not observed in HIF prolyl-hydroxylase inhibitor-treated animals lacking endothelial HIF-2. Taken together, our data indicate that endothelial HIF-2 protects from hypoxia-induced renal damage and represents a potential therapeutic target for renoprotection and prevention of fibrosis following acute ischemic injury. |
