Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin, Tianjin, China.
IUBMB Life. 2011 Jan;63(1):54-61. doi: 10.1002/iub.415.
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-β-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.
肌球蛋白结合蛋白 D 是一种在心肌谱系和出生后发育过程中的平滑肌细胞中特异性表达的非常有效的转录共激活因子。肌球蛋白结合蛋白 D 与广泛表达于胚胎和成年组织中的肌球蛋白相关转录因子 A(MRTF-A)具有同源性。我们之前的研究结果表明肌球蛋白结合蛋白 D 可诱导心肌肥大。然而,MRTF-A 在心肌肥大中的作用仍知之甚少。我们目前的工作进一步表明肌球蛋白结合蛋白 D 在诱导心肌肥大中起重要作用。同时,我们发现过表达新生大鼠心肌细胞中的 MRTF-A 可能诱导心肌细胞肥大。此外,MRTF-A 的表达在苯肾上腺素、血管紧张素-II 和转化生长因子-β刺激的心肌肥大中被诱导,而 MRTF-A 的显性负形式或 MRTF-A siRNA 强烈抑制了对新生大鼠心肌细胞中肥大激动剂的肥大基因的上调。我们的研究表明,除了肌球蛋白结合蛋白 D 之外,MRTF-A 可能在心肌肥大中发挥重要作用。我们的研究结果为进一步研究 MRTFs 在心肌肥大中的作用提供了新的证据。