Kurt, Birguel and Paliege, Alexander and Wiliam, Carsten and Schwarzensteiner, Ilona and Schucht, Kathrin and Neymeyer, Hanna and Sequeira-Lopez, Maria Luisa S. and Bachmann, Sebastian and Gomez, R. Ariel and Eckardt, Kai-Uwe and Kurtz, Armin (2013) Deletion of von Hippel-Lindau Protein Converts Renin-Producing Cells into Erythropoietin-Producing Cells. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 24 (3). pp. 433-444. ISSN 1046-6673,
Full text not available from this repository. (Request a copy)Abstract
States of low perfusion pressure of the kidney associate with hyperplasia or expansion of renin-producing cells, but it is unknown whether hypoxia-triggered genes contribute to these changes. Here, we stabilized hypoxia-inducible transcription factors (HIFs) in mice by conditionally deleting their negative regulator, Vhl, using the Cre/loxP system with renin-1d promoter-driven Cre expression. Vhl(-/-REN) mice were viable and had normal BP. Deletion of Vhl resulted in constitutive accumulation of HIF-2 alpha in afferent arterioles and glomerular cells and HIF-1 alpha in collecting duct cells of the adult kidney. The preglomerular vascular tree developed normally, but far fewer renin-expressing cells were present, with more than 70% of glomeruli not containing renin cells at the typical juxtaglomerular position. Moreover, these mice had an attenuated expansion of renin-producing cells in response to a low-salt diet combined with an ACE inhibitor. However, renin-producing cells of Vhl(-/-REN) mice expressed the erythropoietin gene, and they were markedly polycythemic. Taken together, these results suggest that hypoxia-inducible genes, regulated by VHL, are essential for normal development and physiologic adaptation of renin-producing cells. In addition, deletion of Vhl shifts the phenotype of juxtaglomerular cells from a renin- to erythropoietin-secreting cell type, presumably in response to HIF-2 accumulation. J Am Soc Nephrol 24: 433-444, 2013. doi: 10.1681/ASN.2012080791
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HYPOXIA-INDUCIBLE FACTORS; TUMOR-SUPPRESSOR; INSITU HYBRIDIZATION; ANGIOTENSIN SYSTEM; DEFICIENT MICE; MESSENGER-RNA; MOUSE KIDNEY; EXPRESSION; GENE; OXYGEN; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Apr 2020 04:44 |
| Last Modified: | 24 Apr 2020 04:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17085 |
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