Schoedel, Johannes and Klanke, Bernd and Weidemann, Alexander and Buchholz, Bjoern and Bernhardt, Wanja and Bertog, Marko and Amann, Kerstin and Korbmacher, Christoph and Wiesener, Michael and Warnecke, Christina and Kurtz, Armin and Eckardt, Kai-Uwe and Willam, Carsten (2009) HIF-Prolyl Hydroxylases in the Rat Kidney Physiologic Expression Patterns and Regulation in Acute Kidney Injury. AMERICAN JOURNAL OF PATHOLOGY, 174 (5). pp. 1663-1674. ISSN 0002-9440, 1525-2191
Full text not available from this repository. (Request a copy)Abstract
Hypoxia-inducible transcription factors (HIFs) play important roles in the response of the kidney to systemic and regional hypoxia. Degradation of HIFs is mediated by three oxygen-dependent HIF-prolyl hydroxylases (PHDs), which have partially overlapping characteristics. Although PHD inhibitors, which can induce HIFs in the presence of oxygen, are already in clinical development, little is known about the expression and regulation of these enzymes in the kidney. Therefore, we investigated the expression levels of the three PHDs in both isolated tubular cells and rat kidneys. All three PHDs were present in the kidney and were expressed predominantly in three different cell populations: (a) in distal convoluted tubules and collecting ducts (PHD1,2,3), (b) in glomerular podocytes (PHD1,3), and (c) in interstitial fibroblasts (PHD1,3). Higher levels of PHDs were found in tubular segments of the inner medulla where oxygen tensions are known to be physiologically low. PHD expression levels were unchanged in HIF-positive tubular and interstitial cells after induction by systemic hypoxia. in rat models of acute renal injury, changes in PHD expression levels were variable; while cisplatin and ischemia/reperfusion led to significant decreases in PHD2 and 3 expression levels, no changes were seen in a model of contrast media-induced nephropathy. These results implicate the non-uniform expression of HIF-regulating enzymes that modify the hypoxic response in the kidney under both regional and temporal conditions. (Am J Pathol 2009,174:1663-1674; DOI: 10.2353/ajpath.2009.080687)
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HYPOXIA-INDUCIBLE-FACTOR; ACUTE-RENAL-FAILURE; DOMAIN PROTEINS; MESSENGER-RNA; UP-REGULATION; FACTOR-ALPHA; OXYGEN; ERYTHROPOIETIN; CELLS; INDUCTION; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Sep 2020 04:27 |
| Last Modified: | 16 Sep 2020 04:27 |
| URI: | https://pred.uni-regensburg.de/id/eprint/28991 |
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