Acute hypoxia-induced renal injury often progresses to chronic kidney disease (CKD), and the progressive loss of kidney function in CKD is linked to endothelial cell (EC) damage.
The hypoxia-inducible transcription factors HIF-1 and HIF-2 are expressed in renal ECs following ischemic injury, but the specific contributions of these mediators to pathogenesis are not clear.
In this issue of the Journal of Clinical Investigation, Volker Haase and colleagues at the Vanderbilt University School of Medicine used murine models of hypoxic kidney injury, to evaluate the contribution of endothelial HIF-1 and HIF-2 toward the development of ischemia-induced pathogenesis.
Loss of HIF-2 alone markedly increased kidney inflammation and fibrosis following ischemic injury and was associated with increased expression of the neutrophil adhesion molecule VCAM1.
Blocking VCAM1 in HIF-2-deficient mice reduced hypoxia-associated phenotypes.
Furthermore, enhancing HIF-2 activation in WT mice prior to ischemia and reperfusion protected animals from kidney injury.
Together, these data indicate that endothelial HIF-2 protects kidney from hypoxia-induced damage.