Abstract
RATIONALE:: Cardiomyocytes in adult mammalian hearts are terminally differentiated cells that have exited from the cell cycle and lost most of their proliferative capacity. Death of mature cardiomyocytes in pathological cardiac conditions and the lack of regeneration capacity of adult hearts are primary causes of heart failure and mortality. However, how cardiomyocyte proliferation in postnatal and adult hearts becomes suppressed remains largely unknown. The miR-17-92 cluster was initially identified as a human oncogene that promotes cell proliferation. However, its role in the heart remains unknown. OBJECTIVE:: To test the hypothesis that miR-17-92 participates in the regulation of cardiomyocyte proliferation in postnatal and adult hearts. METHODS AND RESULTS:: We deleted miR-17-92 cluster from embryonic and postnatal mouse hearts and demonstrated that miR-17-92 is required for cardiomyocyte proliferation in the heart. Transgenic overexpression of miR-17-92 in cardiomyocytes is sufficient to induce cardiomyocyte proliferation in embryonic, postnatal, and adult hearts. Moreover, overexpression of miR-17-92 in adult cardiomyocytes protects the heart from myocardial infarction-induced injury. Similarly, we found that members of miR-17-92 cluster, miR-19 in particular, are required for and sufficient to induce cardiomyocyte proliferation in vitro. We identified phosphatase and tensin homolog, a tumor suppressor, as an miR-17-92 target to mediate the function of miR-17-92 in cardiomyocyte proliferation. CONCLUSIONS:: Our studies therefore identify miR-17-92 as a critical regulator of cardiomyocyte proliferation, and suggest this cluster of microRNAs could become therapeutic targets for cardiac repair and heart regeneration.
| Original language | English |
|---|---|
| Pages (from-to) | 1557-1566 |
| Number of pages | 10 |
| Journal | Circulation research |
| Volume | 112 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 2013 Jun 7 |
| Externally published | Yes |
Fingerprint
Keywords
- cardiomyocyte proliferation
- cell cycle
- heart disease
- miR-17-92
- myocardial infarction
- PTEN
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
Cite this
Mir-17-92 cluster is required for and sufficient to induce cardiomyocyte proliferation in postnatal and adult hearts. / Chen, Jinghai; Huang, Zhan Peng; Seok, Hee Young; Ding, Jian; Kataoka, Masaharu; Zhang, Zheng; Hu, Xiaoyun; Wang, Gang; Lin, Zhiqiang; Wang, Si; Pu, Willam T.; Liao, Ronglih; Wang, Da Zhi.
In: Circulation research, Vol. 112, No. 12, 07.06.2013, p. 1557-1566.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mir-17-92 cluster is required for and sufficient to induce cardiomyocyte proliferation in postnatal and adult hearts
AU - Chen, Jinghai
AU - Huang, Zhan Peng
AU - Seok, Hee Young
AU - Ding, Jian
AU - Kataoka, Masaharu
AU - Zhang, Zheng
AU - Hu, Xiaoyun
AU - Wang, Gang
AU - Lin, Zhiqiang
AU - Wang, Si
AU - Pu, Willam T.
AU - Liao, Ronglih
AU - Wang, Da Zhi
PY - 2013/6/7
Y1 - 2013/6/7
N2 - RATIONALE:: Cardiomyocytes in adult mammalian hearts are terminally differentiated cells that have exited from the cell cycle and lost most of their proliferative capacity. Death of mature cardiomyocytes in pathological cardiac conditions and the lack of regeneration capacity of adult hearts are primary causes of heart failure and mortality. However, how cardiomyocyte proliferation in postnatal and adult hearts becomes suppressed remains largely unknown. The miR-17-92 cluster was initially identified as a human oncogene that promotes cell proliferation. However, its role in the heart remains unknown. OBJECTIVE:: To test the hypothesis that miR-17-92 participates in the regulation of cardiomyocyte proliferation in postnatal and adult hearts. METHODS AND RESULTS:: We deleted miR-17-92 cluster from embryonic and postnatal mouse hearts and demonstrated that miR-17-92 is required for cardiomyocyte proliferation in the heart. Transgenic overexpression of miR-17-92 in cardiomyocytes is sufficient to induce cardiomyocyte proliferation in embryonic, postnatal, and adult hearts. Moreover, overexpression of miR-17-92 in adult cardiomyocytes protects the heart from myocardial infarction-induced injury. Similarly, we found that members of miR-17-92 cluster, miR-19 in particular, are required for and sufficient to induce cardiomyocyte proliferation in vitro. We identified phosphatase and tensin homolog, a tumor suppressor, as an miR-17-92 target to mediate the function of miR-17-92 in cardiomyocyte proliferation. CONCLUSIONS:: Our studies therefore identify miR-17-92 as a critical regulator of cardiomyocyte proliferation, and suggest this cluster of microRNAs could become therapeutic targets for cardiac repair and heart regeneration.
AB - RATIONALE:: Cardiomyocytes in adult mammalian hearts are terminally differentiated cells that have exited from the cell cycle and lost most of their proliferative capacity. Death of mature cardiomyocytes in pathological cardiac conditions and the lack of regeneration capacity of adult hearts are primary causes of heart failure and mortality. However, how cardiomyocyte proliferation in postnatal and adult hearts becomes suppressed remains largely unknown. The miR-17-92 cluster was initially identified as a human oncogene that promotes cell proliferation. However, its role in the heart remains unknown. OBJECTIVE:: To test the hypothesis that miR-17-92 participates in the regulation of cardiomyocyte proliferation in postnatal and adult hearts. METHODS AND RESULTS:: We deleted miR-17-92 cluster from embryonic and postnatal mouse hearts and demonstrated that miR-17-92 is required for cardiomyocyte proliferation in the heart. Transgenic overexpression of miR-17-92 in cardiomyocytes is sufficient to induce cardiomyocyte proliferation in embryonic, postnatal, and adult hearts. Moreover, overexpression of miR-17-92 in adult cardiomyocytes protects the heart from myocardial infarction-induced injury. Similarly, we found that members of miR-17-92 cluster, miR-19 in particular, are required for and sufficient to induce cardiomyocyte proliferation in vitro. We identified phosphatase and tensin homolog, a tumor suppressor, as an miR-17-92 target to mediate the function of miR-17-92 in cardiomyocyte proliferation. CONCLUSIONS:: Our studies therefore identify miR-17-92 as a critical regulator of cardiomyocyte proliferation, and suggest this cluster of microRNAs could become therapeutic targets for cardiac repair and heart regeneration.
KW - cardiomyocyte proliferation
KW - cell cycle
KW - heart disease
KW - miR-17-92
KW - myocardial infarction
KW - PTEN
UR - http://www.scopus.com/inward/record.url?scp=84880040358&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84880040358&partnerID=8YFLogxK
U2 - 10.1161/CIRCRESAHA.112.300658
DO - 10.1161/CIRCRESAHA.112.300658
M3 - Article
C2 - 23575307
AN - SCOPUS:84880040358
VL - 112
SP - 1557
EP - 1566
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 12
ER -