Erythropoietin production by PDGFR-?(+) cells

Gerl K, Nolan KA, Karger C, Fuchs M, Wenger RH, Stolt C, Willam C, Kurtz A, Kurt B (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Pflügers Archiv: European Journal of Physiology Springer

Book Volume: 468

Pages Range: 1479-87

Journal Issue: 8

DOI: 10.1007/s00424-016-1829-2

Abstract

PDGFR-?-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-?-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-?(+) 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-?. Amongst a variety of extrarenal organs only adrenal glands showed significant EPO mRNA expression after Vhl deletion in PDGFR-?(+) cells. EPO mRNA, plasma EPO, and hematocrit fell to subnormal values if HIF-2?, but not HIF-1?, was deleted either alone or in combination with Vhl in PDGFR-?(+) 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-1? in PDGFR-?(+) cells but exerted no effect in mice lacking HIF-2? in PDGFR-?(+) cells. These findings suggest that PDGFR-?(+) 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-?(+) cells elaborating EPO might arise from the metanephric mesenchyme, rather than from the neural crest.

Authors with CRIS profile

Claus Stolt Lehrstuhl für Biochemie und Pathobiochemie Carsten Willam Department of Medicine 4 – Nephrology and Hypertension

Involved external institutions

Universität Regensburg DE Germany (DE) University of Zurich / Universität Zürich (UZH) CH Switzerland (CH)

How to cite

APA:

Gerl, K., Nolan, K.A., Karger, C., Fuchs, M., Wenger, R.H., Stolt, C.,... Kurt, B. (2016). Erythropoietin production by PDGFR-?(+) cells. Pflügers Archiv: European Journal of Physiology, 468(8), 1479-87. https://doi.org/10.1007/s00424-016-1829-2

MLA:

Gerl, Katharina, et al. "Erythropoietin production by PDGFR-?(+) cells." Pflügers Archiv: European Journal of Physiology 468.8 (2016): 1479-87.

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