PHGDH
                    Orchestrates Cell Cycle Progression to Drive Cardiomyocyte Proliferation and Myocardial Regeneration via
                    TGF
                    ‐β/Smad Signalling Pathway

Han Zhang; Li Zhang; Zehao Feng; Xing Li; Zhaohui Qiu; Xingyun Wang; Lingmei Qian

doi:10.1111/cpr.70123

journal article Open Access Sep 10, 2025

PHGDH Orchestrates Cell Cycle Progression to Drive Cardiomyocyte Proliferation and Myocardial Regeneration via TGF ‐β/Smad Signalling Pathway

Han Zhang

Li Zhang

Zehao Feng Xing Li

Zhaohui Qiu Xingyun Wang

Lingmei Qian

Cell Proliferation Vol. 59 No. 4 · Wiley

View at Publisher Save 10.1111/cpr.70123

Abstract

ABSTRACT
The mature mammalian heart has limited ability for self‐repair and regeneration. Here, we establish phosphoglycerate dehydrogenase (PHGDH) as a crucial key for cardiomyocyte proliferation, with diminishing expression during postnatal cardiac development. PHGDH overexpression promoted myocardial regeneration and cardiac function in apical resection‐operated mice, whereas inhibition by NCT‐503 inhibited these processes. In vitro, PHGDH stimulated the proliferation of cardiomyocytes (CMs), while NCT‐503 abolished its effect. Mechanistically, PHGDH activated the cell cycle and TGF‐β/Smad signalling. Moreover, PHGDH significantly enhances cardiac repair and stimulates cardiomyocyte proliferation in adult mice following myocardial infarction. Our study demonstrates that upregulating PHGDH promotes CM proliferation and myocardial regeneration, offering a promising therapeutic target for myocardial repair.

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Details

Published: Sep 10, 2025
Vol/Issue: 59(4)
License: View

Authors

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Han Zhang