Gerl, Katharina and Miquerol, Lucile and Todorov, Vladimir T. and Hugo, Christian P. M. and Adams, Ralf H. and Kurtz, Armin and Kurt, Birguel (2015) Inducible glomerular erythropoietin production in the adult kidney. KIDNEY INTERNATIONAL, 88 (6). pp. 1345-1355. ISSN 0085-2538, 1523-1755
Full text not available from this repository. (Request a copy)Abstract
Hypoxia-inducible factor (HIF)-2-triggered erythropoietin production in renal interstitial fibroblast-like cells is the physiologically relevant source of erythropoietin for regulating erythropoiesis. During renal fibrosis, these cells transform into myofibroblasts and lose their ability to produce sufficient erythropoietin leading to anemia. To find if other cells for erythropoietin production might exist in the kidney we tested for the capability of nonepithelial glomerular cells to elaborate erythropoietin. Therefore, HIF transcription factors were stabilized by cell-specific deletion of the von Hippel-Lindau (VHL) gene. Inducible deletion of VHL in glomerular connexin40-expressing cells (endothelial, renin-expressing, and mesangial cells) markedly increased glomerular erythropoietin mRNA expression levels, plasma erythropoietin concentrations, and hematocrit values. These changes were mimicked by inducible cell-specific VHL deletion in renin-expressing and in mesangial cells but not in endothelial cells. The increases of erythropoietin production were absent, when VHL was co-deleted with HIF-2. The induction of glomerular erythropoietin expression was associated with the downregulation of juxtaglomerular renin expression, again in a HIF-2-dependent manner. Thus, VHL deletion in renin-expressing and in mesangial cells induces the capability to produce relevant amounts of erythropoietin and to suppress renin expression in the adult kidney if HIF-2 is stabilized.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ENDOTHELIAL GROWTH-FACTOR; LINDAU TUMOR-SUPPRESSOR; IN-VIVO; PROLYL HYDROXYLASES; EXPERIMENTAL GLOMERULONEPHRITIS; TRANSCRIPTION FACTOR; GENE-EXPRESSION; MESANGIAL CELLS; RENAL FIBROSIS; HIF-ALPHA; cell transformation; erythropoietin; glomerular cells; renin; von Hippel-Lindau |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 May 2019 11:51 |
| Last Modified: | 03 May 2019 11:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4380 |
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