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抑制TGF-β/Smad3信号通路会破坏心室再生过程中的心肌细胞周期进程和上皮-间质转化样反应。

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

作者信息

Peng Yuanyuan, Wang Wenyuan, Fang Yunzheng, Hu Haichen, Chang Nannan, Pang Meijun, Hu Ye-Fan, Li Xueyu, Long Han, Xiong Jing-Wei, Zhang Ruilin

机构信息

School of Life Sciences, Fudan University, Shanghai, China.

Shanghai Medical College, Fudan University, Shanghai, China.

出版信息

Front Cell Dev Biol. 2021 Mar 16;9:632372. doi: 10.3389/fcell.2021.632372. eCollection 2021.

DOI:10.3389/fcell.2021.632372
PMID:33816481
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8010688/
Abstract

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.

摘要

与哺乳动物不同，斑马鱼即使在成年阶段也能再生受损心脏。心脏再生需要心肌细胞（CM）增殖和迁移的协调。TGF-β/Smad3信号通路与心脏再生有关，但该通路调节CM增殖和迁移的分子机制尚未完全阐明。在此，我们在斑马鱼心室消融模型中研究了TGF-β/Smad3信号的功能。损伤后该通路的多个组分被上调/激活。利用Smad3的特异性抑制剂，我们检测到未恢复心脏的比例增加。转录组分析表明，TGF-β/Smad3信号通路可影响CM增殖和迁移。进一步分析表明，CM细胞周期被破坏，上皮-间质转化（EMT）样反应受损，这限制了心脏再生。总之，我们的研究揭示了TGF-β/Smad3信号在斑马鱼心室再生过程中CM细胞周期进程和EMT过程中的重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fe/8010688/841ef1cef690/fcell-09-632372-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fe/8010688/841ef1cef690/fcell-09-632372-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fe/8010688/488e9c63a59e/fcell-09-632372-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fe/8010688/242bb7f8f0ce/fcell-09-632372-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fe/8010688/a8216dad1fd0/fcell-09-632372-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fe/8010688/841ef1cef690/fcell-09-632372-g006.jpg

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