期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 232, 期 12, 页码 3360-3368出版社
WILEY
DOI: 10.1002/jcp.25781
关键词
cardiac hypertrophy; HDAC4; hyperthyroidism; microRNA-1; thyroid hormone
资金
- FAPESP, Foundation for the Support of Research in the State of Sao Paulo [2009/14567-7]
- CNPq, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [472786/2011-3]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [09/14567-7] Funding Source: FAPESP
It is well-known that increased thyroid hormone (TH) levels induce cardiomyocyte growth. MicroRNAs (miRNAs) have been identified as key players in cardiomyocyte hypertrophy, which is associated with increased risk of heart failure. In this study, we evaluated the miR-1 expression in TH-induced cardiac hypertrophy, as well as the potential involvement of miR-1 in cardiomyocyte hypertrophy elicited by TH in vitro. The possible role of type 1 angiotensin II receptor (AT1R) in the effect promoted by TH in miR-1 expression was also evaluated. Neonatal rat cardiac myocytes (NRCMs) were treated with T-3 for 24 hr and Wistar rats were subjected to hyperthyroidism for 14 days combined or not with AT1R blocker. Real Time RT-PCR analysis indicated that miR-1 expression was decreased in cardiac hypertrophy in response to TH in vitro and in vivo, and this effect was unchanged by AT1R blocker. In addition, HDAC4, which is target of miR-1, was increased in NRCMs after T-3 treatment. A gain-of-function study revealed that overexpression of miR-1 prevented T-3-induced cardiomyocyte hypertrophy and reduced HADC4mRNA levels in NRCMs. In vivo experiments confirmed the downregulation of miR-1 in cardiac tissue from hyperthyroid animals, which was accompanied by increased HDAC4 mRNA levels. In addition, HDAC inhibitor prevented T-3-induced cardiomyocyte hypertrophy. Our data reveal a new mechanistic insight into cardiomyocyte growth in response to TH, suggesting that miR-1 plays a role in cardiomyocyte hypertrophy induced by TH potentially via targeting HADC4.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据