Journal
INTERNATIONAL JOURNAL OF CARDIOLOGY
Volume 201, Issue -, Pages 38-48Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.ijcard.2015.06.163
Keywords
miRNA-204; Cardiomyocyte proliferation; Transgenic mice; Jarid2
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Funding
- National Key Basic Research Program fund of China [2013CB531100]
- Fund for National Innovative Research Groups of the National Natural Science Foundation of China [81221001]
- Major International Joint Research Program Fund of China [81120108004]
- General Program of the National Natural Science Foundation of China [81170224, 81270313, 31271214]
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Objectives: In mammals, the heart grows by hypertrophy but not proliferation of cardiomyoc ytes after birth. The paucity of cardiomyocyte proliferation limits cardiac regeneration in a variety of heart diseases. To explore the efficient strategies that drive carcliomyocyte 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. Methods and results: 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. Conclusion: Our findings identify a conserved role for miRNA-204 in regulating cardiomyocyte proliferation by targeting the Jarid2 signaling pathway. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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