Abstract
Objectives
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.
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.
Keywords
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Article info
Publication history
Published online: July 02, 2015
Accepted:
June 29,
2015
Received in revised form:
June 11,
2015
Received:
January 21,
2015
Identification
Copyright
© 2015 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
