Schley, Gunnar and Klanke, Bernd and Schoedel, Johannes and Forstreuter, Frauke and Shukla, Deepa and Kurtz, Armin and Amann, Kerstin and Wiesener, Michael S. and Rosen, Seymour and Eckardt, Kai-Uwe and Maxwell, Patrick H. and Willam, Carsten (2011) Hypoxia-Inducible Transcription Factors Stabilization in the Thick Ascending Limb Protects against Ischemic Acute Kidney Injury. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 22 (11). pp. 2004-2015. ISSN 1046-6673, 1533-3450
Full text not available from this repository. (Request a copy)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-1 alpha 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACUTE-RENAL-FAILURE; TUBULAR EPITHELIAL-CELLS; LINDAU TUMOR-SUPPRESSOR; GENE-EXPRESSION; INTRARENAL OXYGENATION; PROLYL HYDROXYLATION; REPERFUSION INJURY; RAT KIDNEYS; HIF-ALPHA; IN-VIVO; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 May 2020 06:05 |
| Last Modified: | 27 May 2020 06:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19836 |
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