UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

Hypoxia-inducible transcription factors stabilization in the thick ascending limb protects against ischemic acute kidney injury.

Schley, G; Klanke, B; Schödel, J; Forstreuter, F; Shukla, D; Kurtz, A; ... Willam, C; + view all (2011) Hypoxia-inducible transcription factors stabilization in the thick ascending limb protects against ischemic acute kidney injury. J Am Soc Nephrol , 22 (11) 2004 - 2015. 10.1681/ASN.2010121249.

Full text not available from this repository.

Abstract

Hypoxia-inducible transcription factors (HIF) protect cells against oxygen deprivation, and HIF stabilization before ischemia mitigates tissue injury. Because ischemic acute kidney injury (AKI) often involves the thick ascending limb (TAL), modulation of HIF in this segment may be protective. Here, we generated mice with targeted TAL deletion of the von Hippel-Lindau protein (Vhl), which mediates HIF degradation under normoxia, using Tamm-Horsfall protein (Thp)-driven Cre expression. These mice showed strong expression of HIF-1α in TALs but no changes in kidney morphology or function under control conditions. Deficiency of Vhl in the TAL markedly attenuated proximal tubular injury and preserved TAL function following ischemia-reperfusion, which may be partially a result of enhanced expression of glycolytic enzymes and lactate metabolism. These results highlight the importance of the thick ascending limb in the pathogenesis of AKI and suggest that pharmacologically targeting the HIF system may have potential to prevent and mitigate AKI.

Type:Article
Title:Hypoxia-inducible transcription factors stabilization in the thick ascending limb protects against ischemic acute kidney injury.
Location:United States
DOI:10.1681/ASN.2010121249
Language:English
Additional information:PMCID: PMC3279994
Keywords:Acute Kidney Injury, Anaerobic Threshold, Animals, Disease Models, Animal, Erythropoiesis, Glycolysis, Hypoxia-Inducible Factor 1, alpha Subunit, Integrases, Kidney, Loop of Henle, Mice, Mice, Mutant Strains, Nephritis, Reperfusion Injury, Uromodulin, Von Hippel-Lindau Tumor Suppressor Protein
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)

Archive Staff Only: edit this record