Direkt zum Inhalt

Firmke, Bettina K. M. ; Süß, Lena M. ; Forst, Anna‐Lena ; Kurtz, Armin ; Broeker, Katharina A.‐E.

The endocrine product of renal (preglomerular) contractile pericytes depends on prolyl‐4‐hydroxylases 2 and 3

Article

Firmke, Bettina K. M. , Süß, Lena M., Forst, Anna‐Lena , Kurtz, Armin and Broeker, Katharina A.‐E. (2026) The endocrine product of renal (preglomerular) contractile pericytes depends on prolyl‐4‐hydroxylases 2 and 3. The Journal of Physiology.

DOI to cite this document: 10.5283/epub.79410


Abstract

Renal juxtaglomerular renin-producing cells and preglomerular vascular smooth muscle cells (VSMCs) are specialized pericytes with notable plasticity. Preglomerular VSMCs can convert to renin-producing cells during severe hypotension or salt depletion, and renin cells can transform into erythropoietin (EPO)-producing cells when hypoxia‑inducible factor (HIF)-2α is stabilized through deletion of ...

Renal juxtaglomerular renin-producing cells and preglomerular vascular smooth muscle cells (VSMCs) are specialized pericytes with notable plasticity. Preglomerular VSMCs can convert to renin-producing cells during severe hypotension or salt depletion, and renin cells can transform into erythropoietin (EPO)-producing cells when hypoxia‑inducible factor (HIF)-2α is stabilized through deletion of prolyl-4-hydroxylases (PHD) 2 and 3. These findings raise the question of whether PHD2 and PHD3 likewise regulate the endocrine plasticity of preglomerular VSMCs. To investigate the role of PHD2 and/or PHD3 in (preglomerular) contractile pericytes, inducible mouse models with smooth muscle myosin heavy chain (SMMHC)-specific deletion of PHD2 and/or PHD3 were examined under basal conditions or after stimulation of renin production by treating the mice with a low-salt diet and angiotensin converting enzyme inhibitor enalapril (LSE). At baseline, none of the deletions altered renin production or induced EPO expression in preglomerular pericyte-like VSMCs, despite HIF-2α stabilization in PHD2/PHD3-deficient mice. However, HIF-2α stabilization resulting from PHD2 or PHD2/PHD3 deletion triggered EPO production in interstitial SMMHC+ contractile pericytes. LSE treatment induced renin in VSMCs and extraglomerular mesangial cells of control, SMMHCCreERT2 PHD2ff and SMMHCCreERT2 PHD3ff mice. In contrast, VSMCs of PHD2/PHD3-deficient mice produced EPO rather than renin, while renin induction persisted only in mesangial cells. Notably, this LSE-induced EPO production was reversible despite ongoing HIF-2α stabilization. Transcriptional changes indicated a shift in PHD2/PHD3-deficient VSMCs from a contractile/renin cell-like to a contractile/EPO cell-like signature. These findings indicate that HIF-2α stabilization determines the endocrine product of preglomerular VSMCs and interstitial pericytes. Notably, loss of PHD2/PHD3 does not compromise the plasticity of VSMCs to reversibly adopt endocrine functions.



Involved Institutions


Details

Item typeArticle
Journal or Publication TitleThe Journal of Physiology
PublisherWiley
Open Access TypeDEAL (Wiley)
Date4 May 2026
Date of publication06 May 2026 05:06
InstitutionsBiology, Preclinical Medicine > Institut für Physiologie
Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz
Projects
Funded by: Deutsche Forschungsgemeinschaft (DFG) (509149993)
Funded by: Deutsche Forschungsgemeinschaft (DFG) (471535567)
Identification Number
ValueType
10.1113/JP290695DOI
Keywordsendocrine plasticity, erythropoietin, HIF-2α stabilization, pre-glomerular vascular smooth muscle cells, prolyl-4-hydroxylases, renal contractile pericytes, renin
Dewey Decimal Classification500 Science > 500 Natural sciences & mathematics
500 Science > 570 Life sciences
StatusPublished
RefereedYes, this version has been refereed
Created at the University of RegensburgYes
URN of the UB Regensburgurn:nbn:de:bvb:355-epub-794105
Item ID79410

Export bibliographical data

Owner only: item control page

nach oben