Kurt, Birguel and Gerl, Katharina and Karger, Christian and Schwarzensteiner, Ilona and Kurtz, Armin (2015) Chronic Hypoxia-Inducible Transcription Factor-2 Activation Stably Transforms Juxtaglomerular Renin Cells into Fibroblast-Like Cells In Vivo. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 26 (3). pp. 587-596. ISSN 1046-6673, 1533-3450
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On the basis of previous observations that deletion of the von Hippel-Lindau protein (pVHL) in juxtaglomerular (JG) cells of the kidney suppresses renin and induces erythropoietin expression, this study aimed to characterize the events underlying this striking change of hormone expression. We found that renin cell-specific deletion of pVHL in mice leads to a phenotype switch in JG cells, from a cuboid and multiple vesicle-containing form into a flat and elongated form without vesicles. This shift of cell phenotype was accompanied by the disappearance of marker proteins for renin cells (e.g., aldo-keto reductase family 1, member 7 and connexin 40) and by the appearance of markers of fibroblast-like cells (e.g., collagen I, ecto-5'-nucleotidase, and PDGF receptor-beta). Furthermore, hypoxia-inducible transcription factor-2 alpha (HIF-2 alpha) protein constitutively accumulated in these transformed cells. Codeletion of pVHL and HIF-2 alpha in JG cells completely prevented the phenotypic changes. Similar to renin expression in normal JG cells, angiotensin II negatively regulated erythropoietin expression in the transformed cells. In summary, chronic activation of HIF-2 in renal JG cells leads to a reprogramming of the cells into fibroblast-like cells resembling native erythropoietin-producing cells located in the tubulointerstitium.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NECROSIS-FACTOR-ALPHA; ERYTHROPOIETIN GENE-EXPRESSION; LINDAU TUMOR-SUPPRESSOR; NF-KAPPA-B; MESSENGER-RNA; KIDNEY; PROTEIN; INHIBITION; RAT; ECTO-5'-NUCLEOTIDASE; |
| 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 Jul 2019 08:53 |
| Last Modified: | 24 Jul 2019 08:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5919 |
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