Molecular control of vascular smooth muscle cell differentiation
Molecular control of vascular smooth muscle cell differentiation
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DOI：
10.1111/j.1365-201x.1998.tb10706.x
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发表时间：
1998-12-01
期刊：
影响因子：
--
通讯作者：
Owens, GK
中科院分区：
文献类型：
--
作者：
Owens, GK
血管平滑肌细胞(SMC)分化状态的改变，包括生长反应增强、脂代谢改变和基质生成增加，在动脉粥样硬化性疾病的发展中起着关键作用。因此，人们对了解调控血管SMC分化的分子机制和因素，以及这种调控在血管疾病中可能如何被破坏产生了广泛的兴趣。关键问题包括确定控制平滑肌细胞分化功能所需基因的协调表达的机制，以及确定这些调控过程如何受到已知在控制平滑肌分化中重要的局部环境信号的影响。值得注意的是，许多常见的顺式调控元件，包括高度保守的Carg[CC(A/T)(6)GG]基序或类Carg基序，以及转化生长因子(β)调控元件，已在几乎所有迄今已鉴定的平滑肌分化标志基因的启动子中被鉴定，这些基因包括平滑肌α-肌动蛋白、平滑肌肌球蛋白重链、端粒蛋白和SM22α，并被证明是这些基因在体内和体外表达所必需的。此外，研究已经确定了一些与这些顺式元件相互作用的反式因子，并表明这些因子的表达或活性如何受到局部环境信号的影响，如已知影响平滑肌分化的收缩激动剂。
Changes in the differentiated state of the vascular smooth muscle cell (SMC) including enhanced growth responsiveness, altered lipid metabolism, and increased matrix production are known to play a key role in development of atherosclerotic disease. As such, there has been extensive interest in understanding the molecular mechanisms and factors that regulate differentiation of vascular SMC, and how this regulation might be disrupted in vascular disease. Key questions include determination of mechanisms that control the coordinate expression of genes required for the differentiated function of the smooth muscle cell, and determination as to how these regulatory processes are influenced by local environmental cues known to be important in control of smooth muscle differentiation. Of particular interest, a number of common cis regulatory elements including highly conserved CArG [CC(A/T)(6)GG] motifs or CArG-like motifs and a TGF(beta) control element have been identified in the promoters of virtually all smooth muscle differentiation marker genes characterized to date including smooth muscle alpha-actin, smooth muscle myosin heavy chain, telokin, and SM22 alpha and shown to be required for expression of these genes both in vivo and in vitro. In addition, studies have identified a number of trans factors that interact with these cis elements, and shown how the expression or activity of these factors is modified by local environmental cues such as contractile agonists that are known to influence differentiation of smooth muscle.