Wang Da-Zhi, Olson Eric N
Carolina Cardiovascular Biology Center, Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina 27599-7126, USA.
Curr Opin Genet Dev. 2004 Oct;14(5):558-66. doi: 10.1016/j.gde.2004.08.003.
Differentiation of smooth muscle cells (SMCs) is accompanied by the transcriptional activation of an array of muscle-specific genes that confer the unique contractile and physiologic properties of this muscle cell type. The majority of smooth muscle genes are controlled by serum response factor (SRF), a widely expressed transcription factor that also regulates genes involved in cell proliferation. Myocardin and myocardin-related transcription factors (MRTFs) interact with SRF and potently stimulate SRF-dependent transcription. Gain- and loss-of-function experiments have shown myocardin to be sufficient and necessary for SMC differentiation. SMCs are highly plastic and can switch between differentiated and proliferative states in response to extracellular cues. Suppression of SMC differentiation by growth factor signaling is mediated, at least in part, by the displacement of myocardin from SRF by growth factor-dependent ternary complex factors. The association of SRF with myocardin and MRTFs provides a molecular basis for the activation of SMC genes by SRF and the responsiveness of the smooth muscle differentiation program to growth factor signaling.
平滑肌细胞（SMC）的分化伴随着一系列肌肉特异性基因的转录激活，这些基因赋予了这种肌肉细胞类型独特的收缩和生理特性。大多数平滑肌基因由血清反应因子（SRF）控制，SRF是一种广泛表达的转录因子，它也调节参与细胞增殖的基因。心肌素和心肌素相关转录因子（MRTF）与SRF相互作用，并有力地刺激SRF依赖性转录。功能获得和功能丧失实验表明，心肌素对于SMC分化是充分且必要的。SMC具有高度可塑性，能够响应细胞外信号在分化状态和增殖状态之间转换。生长因子信号对SMC分化的抑制至少部分是由生长因子依赖性三元复合因子将心肌素从SRF上置换介导的。SRF与心肌素和MRTF的结合为SRF激活SMC基因以及平滑肌分化程序对生长因子信号的反应性提供了分子基础。
