Inhibition of TGF-β/Smad3 Signaling Disrupts Cardiomyocyte Cell Cycle Progression and Epithelial–Mesenchymal Transition-Like Response During Ventricle Regeneration

Frontiers in Cell and Developmental Biology

Jing-Wei Xiong²  Nannan Chang²  Meijun Pang²  Ruilin Zhang³  Ye-Fan Hu⁴  Xueyu Li⁵  Yuanyuan Peng⁵  Han Long⁵  Wenyuan Wang⁵  Yunzheng Fang⁵  Haichen Hu⁶ 

[1] Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, China;Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing, China;School of Basic Medical Sciences, Wuhan University, Wuhan, China;School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, China;School of Life Sciences, Fudan University, Shanghai, China;Shanghai Medical College, Fudan University, Shanghai, China;

关键词: ventricle regeneration;    TGF-β;    Smad3;    cell cycle;    EMT-like response;   

DOI  :  10.3389/fcell.2021.632372

来源: DOAJ

【 摘 要 】

Unlike mammals, zebrafish can regenerate injured hearts even in the adult stage. Cardiac regeneration requires the coordination of cardiomyocyte (CM) proliferation and migration. The TGF-β/Smad3 signaling pathway has been implicated in cardiac regeneration, but the molecular mechanisms by which this pathway regulates CM proliferation and migration have not been fully illustrated. Here, we investigated the function of TGF-β/Smad3 signaling in a zebrafish model of ventricular ablation. Multiple components of this pathway were upregulated/activated after injury. Utilizing a specific inhibitor of Smad3, we detected an increased ratio of unrecovered hearts. Transcriptomic analysis suggested that the TGF-β/Smad3 signaling pathway could affect CM proliferation and migration. Further analysis demonstrated that the CM cell cycle was disrupted and the epithelial–mesenchymal transition (EMT)-like response was impaired, which limited cardiac regeneration. Altogether, our study reveals an important function of TGF-β/Smad3 signaling in CM cell cycle progression and EMT process during zebrafish ventricle regeneration.

【 授权许可】

Unknown