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	Gata4 regulates fgf16 to promote heart repair after injury
	Yu, Wei1; Huang, Xiuzhen1; Tian, Xueying1; Zhang, Hui1; He, Lingjuan1; Wang, Yue1; Nie, Yu2,3; Hu, Shengshou2,3; Lin, Zhiqiang4; Zhou, Bin1,5,6,7,9,10
刊名	Development
	2016-03-15
卷号	143期号:6页码:936-949
关键词	Heart repair Heart regeneration Cardiomyocyte proliferation Gata4 Fgf16
ISSN号	0950-1991
DOI	10.1242/dev.130971
通讯作者	Zhou, bin(zhoubin@sibs.ac.cn)
英文摘要	Although the mammalian heart can regenerate during the neonatal stage, this endogenous regenerative capacity is lost with age. importantly, replication of cardiomyocytes has been found to be the key mechanism responsible for neonatal cardiac regeneration. unraveling the transcriptional regulatory network for inducing cardiomyocyte replication will, therefore, be crucial for the development of novel therapies to drive cardiac repair after injury. here, we investigated whether the key cardiac transcription factor gata4 is required for neonatal mouse heart regeneration. using the neonatal mouse heart cryoinjury and apical resection models with an inducible loss of gata4 specifically in cardiomyocytes, we found severely depressed ventricular function in the gata4-ablated mice (mutant) after injury. this was accompanied by reduced cardiomyocyte replication. in addition, the mutant hearts displayed impaired coronary angiogenesis and increased hypertrophy and fibrosis after injury. mechanistically, we found that the paracrine factor fgf16 was significantly reduced in the mutant hearts after injury compared with littermate controls and was directly regulated by gata4. cardiac-specific overexpression of fgf16 via adeno-associated virus subtype 9 (aav9) in the mutant hearts partially rescued the cryoinjury-induced cardiac hypertrophy, promoted cardiomyocyte replication and improved heart function after injury. altogether, our data demonstrate that gata4 is required for neonatal heart regeneration through regulation of fgf16, suggesting that paracrine factors could be of potential use in promoting myocardial repair.
WOS关键词	NEONATAL MOUSE HEART ; TRANSCRIPTION FACTORS ; CARDIOMYOCYTE PROLIFERATION ; CARDIAC-FUNCTION ; GROWTH-FACTORS ; IN-VIVO ; KAPPA-B ; REGENERATION ; FGF-16 ; ADULT
WOS研究方向	Developmental Biology
WOS类目	Developmental Biology
语种	英语
出版者	COMPANY OF BIOLOGISTS LTD
WOS记录号	WOS:000384750600005
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2375035
专题	中国科学院大学
通讯作者	Zhou, Bin
作者单位	1.Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, Shanghai 200031, Peoples R China 2.Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing 100037, Peoples R China 3.Peking Union Med Coll, Beijing 100037, Peoples R China 4.Boston Childrens Hosp, Dept Cardiol, 300 Longwood Ave, Boston, MA 02115 USA 5.Yeshiva Univ, Albert Einstein Coll Med, Dept Genet, 1301 Morris Pk Ave, Bronx, NY 10461 USA 6.Yeshiva Univ, Albert Einstein Coll Med, Dept Pediat, 1301 Morris Pk Ave, Bronx, NY 10461 USA 7.Yeshiva Univ, Albert Einstein Coll Med, Dept Med Cardiol, 1301 Morris Pk Ave, Bronx, NY 10461 USA 8.Chinese Univ Hong Kong, Prince Wales Hosp, Li Ka Shing Inst Hlth Sci, Dept Chem Pathol, Shatin 999077, Hong Kong, Peoples R China 9.Chinese Acad Sci, Shanghai Inst Biol Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Inst Neurosci,State Key Lab Neurosci, Shanghai 200031, Peoples R China 10.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
推荐引用方式 GB/T 7714	Yu, Wei,Huang, Xiuzhen,Tian, Xueying,et al. Gata4 regulates fgf16 to promote heart repair after injury[J]. Development,2016,143(6):936-949.
APA	Yu, Wei.,Huang, Xiuzhen.,Tian, Xueying.,Zhang, Hui.,He, Lingjuan.,...&Lui, Kathy O..(2016).Gata4 regulates fgf16 to promote heart repair after injury.Development,143(6),936-949.
MLA	Yu, Wei,et al."Gata4 regulates fgf16 to promote heart repair after injury".Development 143.6(2016):936-949.

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