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Preglomerular VSMCs can convert to renin\u2010producing cells during severe hypotension or salt depletion, and renin cells can transform into erythropoietin (EPO)\u2010producing cells when hypoxia\u2011inducible factor (HIF)\u20102\u03b1 is stabilized through deletion of prolyl\u20104\u2010hydroxylases (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)\u2010specific deletion of PHD2 and\/or PHD3 were examined under basal conditions or after stimulation of renin production by treating the mice with a low\u2010salt diet and angiotensin converting enzyme inhibitor enalapril (LSE). At baseline, none of the deletions altered renin production or induced EPO expression in preglomerular pericyte\u2010like VSMCs, despite HIF\u20102\u03b1 stabilization in PHD2\/PHD3\u2010deficient mice. However, HIF\u20102\u03b1 stabilization resulting from PHD2 or PHD2\/PHD3 deletion triggered EPO production in interstitial SMMHC\n +<\/jats:sup>\n contractile pericytes. LSE treatment induced renin in VSMCs and extraglomerular mesangial cells of control, SMMHC\n CreERT2<\/jats:sup>\n PHD2\n ff<\/jats:sup>\n and SMMHC\n CreERT2<\/jats:sup>\n PHD3\n ff<\/jats:sup>\n mice. In contrast, VSMCs of PHD2\/PHD3\u2010deficient mice produced EPO rather than renin, while renin induction persisted only in mesangial cells. Notably, this LSE\u2010induced EPO production was reversible despite ongoing HIF\u20102\u03b1 stabilization. Transcriptional changes indicated a shift in PHD2\/PHD3\u2010deficient VSMCs from a contractile\/renin cell\u2010like to a contractile\/EPO cell\u2010like signature. These findings indicate that HIF\u20102\u03b1 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.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n Smooth muscle myosin heavy chain (SMMHC)\u2010specific deletion of the prolyl\u20114\u2011hydroxylases PHD2 and PHD3\u00a0stabilized hypoxia\u2011inducible factor (HIF)\u20112\u03b1 in preglomerular pericyte\u2011like vascular smooth muscle cells (VSMCs), prompting a transcriptional shift from a contractile\/renin cell\u2011like toward a more contractile\/EPO cell\u2011like signature without activating erythropoietin (EPO) transcription.<\/jats:p>\n <\/jats:list-item>\n \n A reduction in systolic blood pressure through treatment with low\u2010salt diet and angiotensin converting enzyme inhibitor enalapril induced EPO synthesis instead of renin in preglomerular PHD2\/PHD3\u2010deficient VSMCs. Transformation of preglomerular VSMCs into EPO\u2010producing cells was reversible despite persistent HIF\u20102\u03b1 stabilization.<\/jats:p>\n <\/jats:list-item>\n \n SMMHC cell\u2010specific deletion of PHD2 and PHD2\/PHD3 activated EPO production in interstitial contractile pericytes independent of systolic blood pressure.<\/jats:p>\n <\/jats:list-item>\n \n Short\u2011term HIF\u20112\u03b1 stabilization was insufficient to induce EPO production in preglomerular VSMCs or contractile pericytes.<\/jats:p>\n <\/jats:list-item>\n \n \u03a4aken together these findings demonstrate that HIF\u20102\u03b1 stabilization governs the endocrine output of preglomerular VSMCs and interstitial pericytes. Notably, the loss of PHD2\/PHD3 does not impair the capacity of VSMCs to reversibly assume endocrine functions.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp290695","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T01:15:48Z","timestamp":1777943748000},"page":"5031-5060","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The endocrine product of renal (preglomerular) contractile pericytes depends on prolyl\u20104\u2010hydroxylases 2 and 3"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5960-8231","authenticated-orcid":false,"given":"Bettina K. 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