Sobue K, Hayashi K, Nishida W
Department of Neurochemistry and Neuropharmacology, Biomedical Research Center, Osaka University Medical School, Suita, Japan.
Mol Cell Biochem. 1999 Jan;190(1-2):105-18.
Phenotypic modulation of smooth muscle cells (SMCs) plays an integral role in atherosclerosis, hypertension and leiomyogenic tumorigenicity. The morphological, functional, and biochemical characteristics of SMCs in different phenotypes such as differentiated and dedifferentiated states have been well studied. Recent researches have focused on the expressional regulation of SMC-specific marker genes in association with phenotypic modulation of SMCs. The SMC-specific marker genes are regulated at the levels of transcription and splicing. The caldesmon, smooth muscle myosin heavy chain, alpha-smooth muscle actin, calponin, SM22, alpha- and beta-tropomyosins, and alpha1 integrin genes are transcriptionally regulated; transcription of these genes except for the alpha-smooth muscle actin gene is upregulated in differentiated SMCs, but is downregulated in dedifferentiated SMCs. The expression pattern of alpha-smooth muscle actin is opposite in vascular and visceral SMCs. In almost all promoter regions of these genes, the CArG box and serum response factor (SRF) are involved in as the positive cis-element and the trans-acting factor, respectively. Isoform changes of caldesmon, alpha-tropomyosin, vinculin/metavinculin, and smooth muscle myosin heavy chain are regulated by alternative splicing in a SMC phenotype-dependent manner. Among them, isoform interconversions of caldesmon and alpha-tropomyosin are completely coordinated with phenotype of SMCs. The purpose of this paper is to summarize current knowledge of the expressional regulation of SMC-specific marker genes in different phenotypes of SMCs.
平滑肌细胞（SMC）的表型调节在动脉粥样硬化、高血压和平滑肌源性肿瘤发生中起着不可或缺的作用。不同表型（如分化和去分化状态）的SMC的形态、功能和生化特性已得到充分研究。最近的研究集中在与SMC表型调节相关的SMC特异性标记基因的表达调控上。SMC特异性标记基因在转录和剪接水平上受到调控。钙调蛋白、平滑肌肌球蛋白重链、α-平滑肌肌动蛋白、钙结合蛋白、SM22、α和β-原肌球蛋白以及α1整合素基因受到转录调控；除α-平滑肌肌动蛋白基因外，这些基因的转录在分化的SMC中上调，但在去分化的SMC中下调。α-平滑肌肌动蛋白的表达模式在血管和内脏SMC中相反。在这些基因的几乎所有启动子区域，CArG框和血清反应因子（SRF）分别作为正向顺式元件和反式作用因子参与其中。钙调蛋白、α-原肌球蛋白、纽蛋白/间纽蛋白和平滑肌肌球蛋白重链的异构体变化通过可变剪接以SMC表型依赖的方式受到调控。其中，钙调蛋白和α-原肌球蛋白的异构体相互转换与SMC的表型完全协调。本文的目的是总结SMC不同表型中SMC特异性标记基因表达调控的当前知识。
