title: miRNA-204 drives cardiomyocyte proliferation via targeting Jarid2.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Our findings identify a conserved role for miRNA-204 in regulating cardiomyocyte proliferation by targeting the Jarid2 signaling pathway.
authors: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Research Center for Translational Medicine, Tongji University School of Medicine, Shanghai 200120, China; Institute of Medical Genetics, Tongji University, Shanghai 200092, China.
authors: Dandan
authors: D
authors: Liang
authors: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Research Center for Translational Medicine, Tongji University School of Medicine, Shanghai 200120, China; Institute of Medical Genetics, Tongji University, Shanghai 200092, China.
authors: Jun
authors: J
authors: Li
authors: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai 200092, China.
authors: Yahan
authors: Y
authors: Wu
authors: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai 200092, China.
authors: Lixiao
authors: L
authors: Zhen
authors: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai 200092, China.
authors: Changming
authors: C
authors: Li
authors: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai 200092, China.
authors: Man
authors: M
authors: Qi
authors: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai 200092, China.
authors: Lijie
authors: L
authors: Wang
authors: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai 200092, China.
authors: Fangfei
authors: F
authors: Deng
authors: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai 200092, China.
authors: Jian
authors: J
authors: Huang
authors: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai 200092, China.
authors: Fei
authors: F
authors: Lv
authors: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Research Center for Translational Medicine, Tongji University School of Medicine, Shanghai 200120, China; Institute of Medical Genetics, Tongji University, Shanghai 200092, China.
authors: Yi
authors: Y
authors: Liu
authors: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai 200092, China.
authors: Xiue
authors: X
authors: Ma
authors: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Research Center for Translational Medicine, Tongji University School of Medicine, Shanghai 200120, China.
authors: Zuoren
authors: Z
authors: Yu
authors: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Research Center for Translational Medicine, Tongji University School of Medicine, Shanghai 200120, China.
authors: Yuzhen
authors: Y
authors: Zhang
authors: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Research Center for Translational Medicine, Tongji University School of Medicine, Shanghai 200120, China; Institute of Medical Genetics, Tongji University, Shanghai 200092, China; Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai 200092, China. Electronic address: yihanchen@tongji.edu.cn.
authors: Yi-Han
authors: YH
authors: Chen
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D018390:Gene Targeting / Q000379:methods; D006321:Heart / Q000196:embryology / Q000254:growth & development; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D032383:Myocytes, Cardiac / Q000378:metabolism*; D063151:Polycomb Repressive Complex 2 / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C093650:Jarid2 protein, mouse; C574692:MIRN204 microRNA, mouse; D035683:MicroRNAs; D063151:Polycomb Repressive Complex 2
keywords: Cardiomyocyte proliferation; Jarid2; Transgenic mice; miRNA-204