Erythropoietin production by PDGFR-β(+) cells
| Autor: | Birgül Kurt, Katharina Gerl, C. Claus Stolt, Armin Kurtz, Carsten Willam, Christian Karger, Roland H. Wenger, Karen A. Nolan, Michaela Fuchs |
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| Přispěvatelé: | University of Zurich, Kurt, Birgül |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Physiology Clinical Biochemistry 1308 Clinical Biochemistry expressing cells Kidney 10052 Institute of Physiology Mice 0302 clinical medicine 2737 Physiology (medical) hemic and lymphatic diseases Basic Helix-Loop-Helix Transcription Factors Receptor biology Neural crest medicine.anatomical_structure Von Hippel-Lindau Tumor Suppressor Protein 030220 oncology & carcinogenesis 10076 Center for Integrative Human Physiology embryonic structures Platelet-derived growth factor receptor medicine.drug medicine.medical_specialty PDGFR Mesenchyme β 610 Medicine & health Receptor Platelet-Derived Growth Factor beta 03 medical and health sciences Physiology (medical) Internal medicine medicine HIF Animals RNA Messenger neoplasms Transcription factor Erythropoietin Adrenal gland Messenger RNA Inducible deletion of Vhl Prolyl-Hydroxylase Inhibitors 1314 Physiology Hypoxia-Inducible Factor 1 alpha Subunit 030104 developmental biology Endocrinology biology.protein 570 Life sciences |
| Zdroj: | Pflugers Archiv : European journal of physiology. 468(8) |
| ISSN: | 1432-2013 |
| Popis: | PDGFR-β-expressing cells of the kidneys are considered as a relevant site of erythropoietin (EPO) production. The origin of these cells, their contribution to renal EPO production, and if PDGFR-β-positive cells in other organs are also capable to express EPO are less clear. We addressed these questions in mice, in which hypoxia-inducible transcription factors were stabilized in PDGFR-β(+) cells by inducible deletion of the von Hippel-Lindau (Vhl) protein. Vhl deletion led to a 600-fold increase of plasma EPO concentration, 170-fold increase of renal EPO messenger RNA (mRNA) levels, and an increase of hematocrit values up to 70 %. Intrarenal localization of EPO-expressing cells coincided with the zonal heterogeneity and distribution of cells expressing PDGFR-β. Amongst a variety of extrarenal organs only adrenal glands showed significant EPO mRNA expression after Vhl deletion in PDGFR-β(+) cells. EPO mRNA, plasma EPO, and hematocrit fell to subnormal values if HIF-2α, but not HIF-1α, was deleted either alone or in combination with Vhl in PDGFR-β(+) cells. Treatment of mice with a prolyl-hydroxylase inhibitor caused an increase of EPO mRNA abundance and plasma EPO concentrations in wild-type mice and in mice lacking HIF-1α in PDGFR-β(+) cells but exerted no effect in mice lacking HIF-2α in PDGFR-β(+) cells. These findings suggest that PDGFR-β(+) cells are the only relevant site of EPO expression in the kidney and that HIF-2 is the essential transcription factor triggering EPO expression therein. Moreover, our findings suggest that PDGFR-β(+) cells elaborating EPO might arise from the metanephric mesenchyme, rather than from the neural crest. |
| Databáze: | OpenAIRE |
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