Abstract
Arterial smooth muscle cells (SMCs) play a major role in atherosclerosis and restenosis. Differential display was used to compare transcription profiles of synthetic SMCs to proliferating rat cultured SMC line. An isolated cDNA band (6A3-5) was shown by northern (7 kb) to be upregulated in the proliferating cell line. A rat tissue northern showed differential expression of this gene in different tissues. Using 5′ RACE and screening of a rat brain library, part of the cDNA was cloned and sequenced (5.4 kb). Sequence searches showed important similarities with a new family of transcription factors, bearing ARID motifs. A polyclonal antibody was raised and showed a protein band of 175 kd, which is localized intracellularly. We also showed that 6A3-5 is upregulated in dedifferentiated SMC (P9) in comparison to contractile SMC ex vivo (P0). This work describes cloning, structural, and functional characterization of a new early gene involved in SMC phenotype modulation.
Highlights
Migration and proliferation of smooth muscle cells (SMCs) into the intima plays a key role in the initiation and perpetuation of atherosclerotic lesions [1, 2, 3]
We have identified for the first time a new 7 kb transcription factor gene (6A3-5) that is overexpressed in proliferating, but not synthetic, rat smooth muscle cells
Several lines of evidence back the above statement: (1) differential display shows an upregulation of 6A3-5 in proliferating but not synthetic SMCs
Summary
Migration and proliferation of smooth muscle cells (SMCs) into the intima plays a key role in the initiation and perpetuation of atherosclerotic lesions [1, 2, 3]. According to Ross [4], proliferation of SMCs in atherosclerotic lesions is the result of an excessive inflammatory fibroproliferative response to various forms of insult to the endothelium. In these diseased vessel walls, SMCs undergo a phenotypic modulation [5, 6] where they change from a highly contractile, fully differentiated, state to a synthetic and/or proliferating dedifferentiated phenotype [4, 7, 8]. SMCs are transformed into foam cells by. In long-term cultures, aortic SMCs generate a proliferating transformed phenotype [13, 14] with similarities to proliferating cells [15]
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