Publication in refereed journal
香港中文大学研究人员 ( 现职)
| 吕爱兰教授 (化学病理学系) |
全文
| 数位物件识别号 (DOI) http://dx.doi.org/10.1242/dev.130971 |
引用次数
Web of Sciencehttp://aims.cuhk.edu.hk/converis/portal/Publication/7WOS source URL
Scopushttp://aims.cuhk.edu.hk/converis/portal/Publication/6Scopus source URL
其它资讯
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 FGF1http://aims.cuhk.edu.hk/converis/portal/Publication/6 was significantly reduced in the mutant hearts after injury compared with littermate controls andwas directly regulated byGATA4. Cardiac-specific overexpression of FGF1http://aims.cuhk.edu.hk/converis/portal/Publication/6 via adeno-associated virus subtype 9 (AAV9) in the mutant hearts partially rescued the cryoinjuryinduced 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 Fgf1http://aims.cuhk.edu.hk/converis/portal/Publication/6, suggesting that paracrine factors could be of potential use in promoting myocardial repair.
着者Yu W., Huang X., Tian X., Zhang H., He L., Wang Y., Nie Y., Hu S., Lin Z., Zhou B., Pu W., Lui K.O., Zhou B.
期刊名称Development
出版年份201http://aims.cuhk.edu.hk/converis/portal/Publication/6
月份3
日期15
卷号143
期次http://aims.cuhk.edu.hk/converis/portal/Publication/6
出版社The Company of Biologists Ltd.
出版地United Kingdom
页次93http://aims.cuhk.edu.hk/converis/portal/Publication/6 - 949
国际标準期刊号0950-1991
电子国际标準期刊号14http://aims.cuhk.edu.hk/converis/portal/Publication/7http://aims.cuhk.edu.hk/converis/portal/Publication/7-9129
语言英式英语
关键词Cardiomyocyte proliferation, FGF1http://aims.cuhk.edu.hk/converis/portal/Publication/6, GATA4, Heart regeneration, Heart repair
