Critical Role of miR-130b-5p in Cardiomyocyte Proliferation and Cardiac Repair in Mice After Myocardial Infarction
Critical Role of miR-130b-5p in Cardiomyocyte Proliferation and Cardiac Repair in Mice After Myocardial Infarction
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DOI：
10.1093/stmcls/sxad080
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发表时间：
2024-01-13
期刊：
影响因子：
5.2
通讯作者：
Kang，Jiuhong
中科院分区：
文献类型：
--
作者：
Feng，Ke;Wu，Yukang;Kang，Jiuhong
成年心肌细胞增殖能力差是心肌梗死后心力衰竭的主要原因，因此探索促进成年心肌细胞增殖的分子和机制对心肌梗死后心脏修复具有重要意义。在这里，我们发现miR-130 b-5 p在小鼠胚胎和新生儿心脏中高度表达，并且能够在体外和体内促进心肌细胞增殖。机制研究表明，miR-130 b-5 p主要通过MAPK-ERK信号通路促进心肌细胞增殖，而MAPK-ERK信号通路的负调控因子Dusp 6是miR-130 b-5 p的直接作用靶点。此外，我们发现过表达miR-130 b-5 p可以促进MI后小鼠心肌细胞的增殖，改善心功能。这些研究揭示了miR-130 b-5 p及其靶向MAPK-ERK信号在成年心脏心肌细胞增殖中的关键作用，并证明miR-130 b-5 p可能是MI后心脏修复的潜在靶点。
Poor proliferative capacity of adult cardiomyocytes is the primary cause of heart failure after myocardial infarction (MI), thus exploring the molecules and mechanisms that promote the proliferation of adult cardiomyocytes is crucially useful for cardiac repair after MI. Here, we found that miR-130b-5p was highly expressed in mouse embryonic and neonatal hearts and able to promote cardiomyocyte proliferation both in vitro and in vivo. Mechanistic studies revealed that miR-130b-5p mainly promoted the cardiomyocyte proliferation through the MAPK-ERK signaling pathway, and the dual-specific phosphatase 6 (Dusp6), a negative regulator of the MAPK-ERK signaling, was the direct target of miR-130b-5p. Moreover, we found that overexpression of miR-130b-5p could promote the proliferation of cardiomyocytes and improve cardiac function in mice after MI. These studies thus revealed the critical role of miR-130b-5p and its targeted MAPK-ERK signaling in the cardiomyocyte proliferation of adult hearts and proved that miR-130b-5p could be a potential target for cardiac repair after MI.