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Updated: May 13, 2025

Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
β-adrenergic receptor inhibits heart regeneration by downregulating Yap m6A modification
Kaihang Guan1, Zijian Li2,3
1Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing Key Laboratory of Cardiovascular Receptors Research, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases, Chinese Academy of Medical Sciences, Beijing, China.
Abstract:
Newborn mammals transiently maintain the heart regenerative capacity. β-adrenergic receptor (β-AR) is the most critical receptor in regulating cardiomyocyte behavior. However, the role and mechanism of β-AR, especially the subtypes of β-AR, in heart regeneration remain unclear. Here, we reveal that β-AR inhibits heart regeneration by downregulating Yap m6A modification. The β-AR expression is associated with heart regenerative capacity. After apical resection, β-AR (including β1-AR and β2-AR) inhibits heart regeneration. β2-AR exerts a more potent inhibitory effect compared with β1-AR. Mechanistically, both β1-AR and β2-AR downregulate Yap m6A modification and then YAP expression differentially by reducing METTL14 and IGF2BP1, respectively. Elevation of Yap m6A modification with adenoviruses encoding METTL14 and IGF2BP1 rescues YAP expression and cardiomyocyte proliferation inhibited by β1-AR and β2-AR, respectively. These findings indicate that both β1-AR and β2-AR inhibit heart regeneration in a m6A-dependent manner and reveal subtype-specific mechanism. These results will provide a new intervention strategy for heart regeneration.
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