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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.
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Details
| Item type | Article | ||||
| Journal or Publication Title | The Journal of Physiology | ||||
| Publisher | Wiley | ||||
| Open Access Type | DEAL (Wiley) | ||||
| Date | 4 May 2026 | ||||
| Date of publication | 06 May 2026 05:06 | ||||
| Institutions | Biology, 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 |
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| Keywords | endocrine plasticity, erythropoietin, HIF-2α stabilization, pre-glomerular vascular smooth muscle cells, prolyl-4-hydroxylases, renal contractile pericytes, renin | ||||
| Dewey Decimal Classification | 500 Science > 500 Natural sciences & mathematics 500 Science > 570 Life sciences | ||||
| Status | Published | ||||
| Refereed | Yes, this version has been refereed | ||||
| Created at the University of Regensburg | Yes | ||||
| URN of the UB Regensburg | urn:nbn:de:bvb:355-epub-794105 | ||||
| Item ID | 79410 |
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