Loss of microRNA-128 promotes cardiomyocyte proliferation and heart regeneration

Huang，Wei1,2; Feng，Yuliang1; Liang，Jialiang2; Yu，Hao2; Wang，Cheng3; Wang，Boyu4; Wang，Mingyang5; Jiang，Lin2; Meng，Wei6; Cai，Wenfeng2; Medvedovic，Mario7; Chen，Jenny7; Paul，Christian2; Davidson，W. Sean2; Sadayappan，Sakthivel8; Stambrook，Peter J.9; Yu，Xi Yong1; Wang，Yigang2

2018-12-01

10.1038/s41467-018-03019-z

Nature Communications   影响因子和分区

2041-1723

The goal of replenishing the cardiomyocyte (CM) population using regenerative therapies following myocardial infarction (MI) is hampered by the limited regeneration capacity of adult CMs, partially due to their withdrawal from the cell cycle. Here, we show that microRNA-128 (miR-128) is upregulated in CMs during the postnatal switch from proliferation to terminal differentiation. In neonatal mice, cardiac-specific overexpression of miR-128 impairs CM proliferation and cardiac function, while miR-128 deletion extends proliferation of postnatal CMs by enhancing expression of the chromatin modifier SUZ12, which suppresses p27 (cyclin-dependent kinase inhibitor) expression and activates the positive cell cycle regulators Cyclin E and CDK2. Furthermore, deletion of miR-128 promotes cell cycle re-entry of adult CMs, thereby reducing the levels of fibrosis, and attenuating cardiac dysfunction in response to MI. These results suggest that miR-128 serves as a critical regulator of endogenous CM proliferation, and might be a novel therapeutic target for heart repair.

英语

非南科大

National Natural Science Foundation of China[81330007];National Institutes of Health[HL107957];National Institutes of Health[HL110740];National Institutes of Health[HL130042];National Institutes of Health[HL136025];National Natural Science Foundation of China[U1601227];

2-s2.0-85042224690

Scopus

1.Key Laboratory of Molecular Target and Clinical Pharmacology,School of Pharmaceutical Sciences and Fifth Affiliated Hospital,Guangzhou Medical University,Guangzhou, Guangdong,511436,China
2.Department of Pathology and Laboratory Medicine,University of Cincinnati College of Medicine,Cincinnati,45267,United States
3.Department of Molecular Biology,Radboud Institute of Molecular Life Sciences,Faculty of Science,Radboud University,Nijmegen, Gelderland,6525,Netherlands
4.Samaritan Medical Center,Watertown,830 Washington Street,13601,United States
5.College of Engineering and Applied Science,University of Cincinnati,Cincinnati,45221,United States
6.Division of Liver Surgery,Third Affiliated Hospital of Sun Yat-sen University,Guangzhou, Guangdong,510630,China
7.Department of Environmental Health,University of Cincinnati College of Medicine,Cincinnati,45267,United States
8.Division of Cardiovascular Health and Disease,Department of Internal Medicine,Heart,Lung and Vascular Institute,University of Cincinnati College of Medicine,Cincinnati,45267,United States
9.Department of Molecular Genetics,Biochemistry,and Microbiology,University of Cincinnati College of Medicine,Cincinnati,45267,United States

Huang，Wei,Feng，Yuliang,Liang，Jialiang,et al. Loss of microRNA-128 promotes cardiomyocyte proliferation and heart regeneration[J]. Nature Communications,2018,9(1).

Huang，Wei.,Feng，Yuliang.,Liang，Jialiang.,Yu，Hao.,Wang，Cheng.,...&Wang，Yigang.(2018).Loss of microRNA-128 promotes cardiomyocyte proliferation and heart regeneration.Nature Communications,9(1).

Huang，Wei,et al."Loss of microRNA-128 promotes cardiomyocyte proliferation and heart regeneration".Nature Communications 9.1(2018).