Myocardin-Related Transcription Factor-A Induces Cardiomyocyte Hypertrophy
Myocardin-Related Transcription Factor-A Induces Cardiomyocyte Hypertrophy
复制标题
心肌素相关转录因子 A 诱导心肌细胞肥大
DOI：
10.1002/iub.415
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发表时间：
2011-01-01
期刊：
影响因子：
4.6
通讯作者：
Zhang, Tong-Cun
中科院分区：
文献类型：
--
作者：
Liao, Xing-Hua;Wang, Nan;Zhang, Tong-Cun
肌心素是一种非常有效的转录辅激活因子，在出生后发育过程中特异性表达于心肌谱系和平滑肌细胞。肌红蛋白与肌红蛋白相关转录因子A（MRTF-A）具有同源性，后者在广泛的胚胎和成人组织中表达。我们以前的研究结果表明，心肌素诱导心肌肥大。然而，MRTF-A在心脏肥大中的作用仍然知之甚少。我们目前的工作进一步表明，心肌素在诱导肥大中起着重要作用。同时，我们发现MRTF-A在新生大鼠心肌细胞中的过表达可能会诱导心肌细胞肥大。此外，MRTF-A表达诱导苯肾上腺素，血管紧张素-II，和转化生长因子-β刺激的心肌肥大，而显性负性形式的MRTF-A或MRTF-A siRNA强烈抑制肥大基因的上调，在新生大鼠心肌细胞肥大激动剂。我们的研究表明，除了myocardin，MRTF-A可能在心肌肥厚中发挥重要作用。本研究为进一步探讨MRTFs在心肌肥厚中的作用提供了新的证据。(C)2011 IUBMB IUBMB Life，63（1）：54-61，2011
Myocardin is a remarkably potent transcriptional coactivator expressed specifically in cardiac muscle lineages and smooth muscle cells during postnatal development. Myocardin shares homology with myocardin-related transcription factor-A (MRTF-A), which are expressed in a broad range of embryonic and adult tissues. Our previous results show that myocardin induces cardiac hypertrophy. However, the effects of MRTF-A in cardiac hypertrophy remain poorly understood. Our present work further demonstrates that myocardin plays an important role in inducing hypertrophy. At the same time, we find that overexpression of MRTF-A in neonatal rat cardiomyocytes might induce cardiomyocyte hypertrophy. Furthermore, MRTF-A expression is induced in phenylephrine, angiotensin-II, and transforming growth factor-beta-stimulated cardiac hypertrophy, whereas a dominant-negative form of MRTF-A or MRTF-A siRNA strongly inhibited upregulation of hypertrophy genes in response to hypertrophic agonists in neonatal rat cardiomyocytes. Our studies indicate that besides myocardin, MRTF-A might play an important role in cardiac hypertrophy. Our findings provide novel evidence for the future studies to explore the roles of MRTFs in cardiac hypertrophy. (C) 2011 IUBMB IUBMB Life, 63(1): 54-61, 2011