Schoedel, Johannes and Bohr, Daniela and Klanke, Bernd and Schley, Gunnar and Schloetzer-Schrehardt, Ursula and Warnecke, Christina and Kurtz, Armin and Amann, Kerstin and Eckardt, Kai-Uwe and Willam, Carsten (2010) Factor inhibiting HIF limits the expression of hypoxia-inducible genes in podocytes and distal tubular cells. KIDNEY INTERNATIONAL, 78 (9). pp. 857-867. ISSN 0085-2538,
Full text not available from this repository. (Request a copy)Abstract
The two hypoxia-inducible factors (HIF-1 alpha and HIF-2 alpha) are transcription factors that regulate the response to hypoxia. Recently, the factor inhibiting HIF (FIH1) was identified as a molecular oxygen-dependent dioxygenase that blunts the transcriptional activity of HIF and has also been implicated in HIF-dependent and -independent hypoxia responses. Interestingly, HIF accumulation in the kidney has been shown to confer renal protection and to also cause glomerular injury or enhance renal fibrosis. In order to better understand the regulation of hypoxia-inducible genes, we determined the expression of FIH1 in the kidney and its functional role in isolated renal cells. FIH1 was expressed only in distal tubules and in podocytes, thus showing a very distinct expression pattern, partially overlapping with sites of HIF-1 alpha expression. In tubular cells, RNA silencing of FIH1 caused transcriptional activation of HIF target genes during hypoxia. In contrast, FIH1 silencing in podocytes enhanced transcription of hypoxia-inducible genes in an HIF-independent manner. Using the anti-Thy. 1 rat model of glomerulonephritis, we found a gradual decrease of glomerular FIH1 expression during disease progression paralleled by an increase in hypoxia-inducible genes including CXCR4, a mediator of glomerular inflammation. Thus, FIH1 appears to be a suppressor of oxygen-dependent genes in the kidney, operating through HIF-dependent and -independent mechanisms. Kidney International (2010) 78, 857-867; doi:10.1038/ki.2010.284; published online 18 August 2010
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ERYTHROPOIETIN-PRODUCING CELLS; ACUTE-KIDNEY-INJURY; ASPARAGINYL HYDROXYLASE; TRANSCRIPTIONAL ACTIVITY; RAT KIDNEYS; FACTOR FIH; IN-VIVO; PATHWAY; MICE; RNA; cell biology and structure; hypoxia; immunohistochemistry; podocyte; tubule cells |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Jul 2020 10:16 |
| Last Modified: | 07 Jul 2020 10:16 |
| URI: | https://pred.uni-regensburg.de/id/eprint/23966 |
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