biostudies-literatureUnknown24(11)Fahling MRenal hypoxia occurs in AKI of various etiologies, but adaptation to hypoxia, mediated by hypoxia-inducible factor (HIF), is incomplete in these conditions. Preconditional HIF activation protects against renal ischemia-reperfusion injury, yet the mechanisms involved are largely unknown, and HIF-mediated renoprotection has not been examined in other causes of AKI. Here, we show that selective activation of HIF in renal tubules, through Pax8-rtTA-based inducible knockout of von Hippel-Lindau protein (VHL-KO), protects from rhabdomyolysis-induced AKI. In this model, HIF activation correlated inversely with tubular injury. Specifically, VHL deletion attenuated the increased levels of serum creatinine/urea, caspase-3 protein, and tubular necrosis induced by rhabdomyolysis in wild-type mice. MorJournal of the American Society of Nephrology : JASN1806-19https://www.ebi.ac.uk/biostudies/studies/S-EPMC3810090biostudies-literatureTubular von Hippel-Lindau knockout protects against rhabdomyolysis-induced AKI.PMC3810090Mathia SPaliege APeters HNeumayer HHFahling MPersson PBKoesters RMrowka RBachmann SRosenberger CfalseTubular von Hippel-Lindau knockout protects against rhabdomyolysis-induced AKI.Renal hypoxia occurs in AKI of various etiologies, but adaptation to hypoxia, mediated by hypoxia-inducible factor (HIF), is incomplete in these conditions. Preconditional HIF activation protects against renal ischemia-reperfusion injury, yet the mechanisms involved are largely unknown, and HIF-mediated renoprotection has not been examined in other causes of AKI. Here, we show that selective activation of HIF in renal tubules, through Pax8-rtTA-based inducible knockout of von Hippel-Lindau protein (VHL-KO), protects from rhabdomyolysis-induced AKI. In this model, HIF activation correlated inversely with tubular injury. Specifically, VHL deletion attenuated the increased levels of serum creatinine/urea, caspase-3 protein, and tubular necrosis induced by rhabdomyolysis in wild-type mice. Mor2013-01-01T00:00:00Z2013 Nov2026-05-04T19:33:51.298Z2026-04-07T20:55:04.516ZS-EPMC38100902397012510.1681/ASN.201303028110.1681/asn.2013030281