Gerl, Katharina and Steppan, Dominik and Fuchs, Michaela and Wagner, Charlotte and Willam, Carsten and Kurtz, Armin and Kurt, Birguel (2017) Activation of Hypoxia Signaling in Stromal Progenitors Impairs Kidney Development. AMERICAN JOURNAL OF PATHOLOGY, 187 (7). pp. 1496-1511. ISSN 0002-9440, 1525-2191
Full text not available from this repository. (Request a copy)Abstract
Intrauterine hypoxia is a reason for impaired kidney development. The cellular and molecular pathways along which hypoxia exerts effects on nephrogenesis are not well understood. They are likely triggered by hypoxia-inducible transcription factors (HIFs), and their effects appear to be dependent on the cell compartment contributing to kidney formation. In this study, we investigated the effects of HIF activation in the developing renal stroma, which also essentially modulates nephron development from the metanephric mesenchyme. HIF activation was achieved by conditional deletion of the von Hippel Lindau tumor suppressor (VHL) protein in the forkhead box FOXD1 cell Lineage, from which stromal progenitors arise. The resulting kidneys showed maturation defects associated with early postnatal death. In particular, nephron formation, tubular maturation, and the differentiation of smooth muscle, renin, and mesangial cells were impaired. Erythropoietin expression was strongly enhanced. CodeLetion of VHL together with HIF2A but not with HIF1A Led to apparently normal kidneys, and the animals reached normal age but were anemic because of low erythropoietin levels. Stromal deletion of HIF2A or HIF1A alone did not affect kidney development. These findings emphasize the relevance of sufficient intrauterine oxygenation for normal renal stroma differentiation, suggesting that chronic activity of HIF2 in stromal progenitors impairs kidney development. Finally, these data confirm the concept that normal stroma function is essential for normal tubular differentiation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LINDAU TUMOR-SUPPRESSOR; GSDM FAMILY GENES; BRANCHING MORPHOGENESIS; MAMMALIAN KIDNEY; EXPERIMENTAL GLOMERULONEPHRITIS; INDUCIBLE FACTOR-1-ALPHA; NEPHRON DIFFERENTIATION; RENAL ERYTHROPOIETIN; GROWTH-FACTOR; MOUSE KIDNEY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:16 |
| Last Modified: | 19 Feb 2019 11:17 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1628 |
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