International Journal of Cardiology 2015-12-15

miRNA-204 drives cardiomyocyte proliferation via targeting Jarid2.

Dandan Liang, Jun Li, Yahan Wu, Lixiao Zhen, Changming Li, Man Qi, Lijie Wang, Fangfei Deng, Jian Huang, Fei Lv, Yi Liu, Xiue Ma, Zuoren Yu, Yuzhen Zhang, Yi-Han Chen

文献索引：Int. J. Cardiol. 201 , 38-48, (2015)

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摘要

In mammals, the heart grows by hypertrophy but not proliferation of cardiomyocytes after birth. The paucity of cardiomyocyte proliferation limits cardiac regeneration in a variety of heart diseases. To explore the efficient strategies that drive cardiomyocyte proliferation, we employed in vitro and in vivo models to investigate the function of miRNA-204, which was demonstrated to regulate the proliferation and differentiation of human cardiac progenitor cells in our previous study.miRNA-204 overexpression markedly promoted cardiomyocyte proliferation in both neonatal and adult rat cardiomyocytes in vitro. Transgenic mice with the cardiac-specific overexpression of miRNA-204 exhibited excessive cardiomyocyte proliferation throughout the embryonic and adult stages, leading to a pronounced increase in ventricular mass. Accordingly, the cell cycle regulators, including Cyclin A, Cyclin B, Cyclin D2, Cyclin E, CDC2 and PCNA, were upregulated in miRNA-204 transgenic embryonic hearts. Furthermore, we demonstrated that miRNA-204 directly targeted Jarid2. Knockdown of Jarid2 mimicked the pro-proliferative effect of miRNA-204 overexpression on cultured rat cardiomyocytes, whereas enhanced expression of Jarid2 conferred the myocytes with substantial resistance to proliferation by miRNA-204 overexpression.Our findings identify a conserved role for miRNA-204 in regulating cardiomyocyte proliferation by targeting the Jarid2 signaling pathway.Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.