Expressional regulation of smooth muscle cell-specific genes in association with phenotypic modulation

Phenotypic modulation of smooth muscle cells (SMCs) plays an integral role in atherosclerosis, hypertension and leiomyogenic tumorigenicity. The morph ological, functional, and biochemical characteristics of SMCs in different phenotypes such as differentiated and dedifferentiated states have been wel l studied. Recent researches have focused on the expressional regulation of SMC-specific marker genes in association with phenotypic modulation of SMC s. The SMC-specific marker gems are regulated at the levels of transcriptio n and splicing. The caldesmon, smooth muscle myosin heavy chain, alpha-smoo th muscle actin, calponin, SM22, alpha- and beta-tropomyosins, and alpha 1 integrin genes are transcriptionally regulated; transcription of these gene s except for the alpha-smooth muscle actin gene is upregulated in different iated SMCs, but is downregulated in dedifferentiated SMCs. The expression p attern of alpha-smooth muscle actin is opposite in vascular and visceral SM Cs. In almost all promoter regions of these genes, the CArG box and serum r esponse factor (SRF) are involved in as the positive cis-element and the tr ans-acting factor, respectively. Isoform changes of caldesmon, alpha-tropom yosin, vinculin/metavinculin, and smooth muscle myosin heavy chain are regu lated by alternative splicing in a SMC phenotype-dependent manner. Among th em, isoform interconversions of caldesmon and alpha-tropomyosin are complet ely coordinated with phenotype of SMCs. The purpose of this paper is to sum marize current knowledge of the expressional regulation of SMC-specific mar ker genes in different phenotypes of SMCs. (Mol Cell Biochem 190: 105-118, 1999).