Myocardin: A component of a molecular switch for smooth muscle differentiation
Myocardin: A component of a molecular switch for smooth muscle differentiation
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DOI：
10.1006/jmcc.2002.2086
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发表时间：
2002-10-01
影响因子：
5
通讯作者：
Miano, JM
中科院分区：
文献类型：
--
作者：
Chen, JY;Kitchen, CM;Miano, JM
培养物和受伤的血管壁中平滑肌细胞（SMC）的标志是它们从分化状态到增长，迁移和基质合成的一种表型调节。该遗传程序改变的基础的转录机制尚未阐明。血清反应因子（SRF）通过与近端CARG元素的相互作用而成为SMC限制基因表达的关键调节剂。但是，在SMC表型调制过程中，SRF蛋白的水平不会变化，这表明在此过程中其他因素或事件的作用。这样一个因素可能是心肌，这是一种新型的SRF共激活剂，最近从心脏组织克隆。在大鼠主动脉培养基和关键的SMC限制基因中，心肌素的水平大量表达。在几条SMC线中。心肌mRNA水平与SMC标记表达的损失或衰减并行下降。在SMC和非SMC中，用CMV驱动的肌动蛋白进行的瞬时转染实验揭示了SM-CALP启动子增强剂的CARG依赖性反式激活。其他几个依赖CARG的SMC启动子以细胞和启动子依赖性方式显示可变激活。为了确定心肌素是否可以激活SMC分化的内源性程序，我们稳定地转染了L6成肌细胞并评估了SMC标记表达和生长。结果揭示了与生长潜力较低的几种SMC标记的表达。总的来说，这些研究表明，心肌是SMC分化程序的分子开关的重要组成部分。 （C）2002年由Elsevier Science Ltd.出版。
A hallmark of smooth muscle cells (SMCs) in culture and the injured vessel wall is their phenotypic modulation from a differentiated state to one of heightened growth, migration, and matrix synthesis. The transcriptional mechanisms underlying this altered genetic program have yet to be elucidated. Serum response factor (SRF) has emerged as a critical regulator of SMC-restricted gene expression via its interaction with proximal CArG elements; however, levels of SRF protein do not change during SMC phenotypic modulation, suggesting a role for other factors or events in this process. One such factor could be myocardin, a novel SRF coactivator recently cloned from cardiac tissue. Levels of myocardin are abundantly expressed in rat aortic media along with key SMC-restricted genes. In several SMC lines. myocardin mRNA levels decrease in parallel with the loss or attenuation of SMC marker expression. Transient transfection experiments with CMV-driven myocardin in both SMC and non-SMC reveal CArG-dependent transactivation of the SM-Calp promoter-enhancer. Several additional CArG-dependent SMC promoters show variable activation in a cell-and promoter-context dependent manner. To determine whether myocardin could activate an endogenous program of SMC differentiation, we stably transfected L6 myoblasts and assessed SMC marker expression and growth. Results reveal the expression of several SMC markers concomitant with a lower growth potential. Collectively, these studies suggest that myocardin is an important component of a molecular switch for the SMC differentiation program. (C) 2002 Published by Elsevier Science Ltd.