Studies on molecular biology of phenotype change of smooth muscle cells

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1. Modulation of phenotype of smooth muscle cells: Cultured endothelial cells and macrophages modulated cultured rabbit aortic smooth muscle cells(SMC) through secretion of platelet-derived growth factor(PDGF). Of PDGF isomers, PDGF -BB and -AB but not -AA were the phenotype modulation factors. By these phenotype modulation SMC acquired the following characteristics; 1. rapid growth. 2. expression of scavenger receptors. 3. secretion of SMC derived growth factor(S DGF).2. Phenotype modulation by a ballooning model: Cultured SMC from rabbit aorta treated with a balloon catheter were examined for their phenotype change as a function of time. One day after ballooning SMC phenotype was not changed. But 3 days after SMC growth became rapid. 7 days after SMC showed all characteristics mentioned above. At this time point no intimal layer was formed, indicating that phenotype change occurs in the media.3. Expression of the scavenger receptors in SMC: Scavenger receptors were induced in SMC by treatment with phorbol ester. The mechanism of induction was through release of lysolecithin by activation of phospholipase A2 but not through activation of protein kinase C.4. Characterization of SDGF: The growth activity of SDGF was inhibited by a polyclonal antibody to basic FGF. But western blot analysis showed that the molecular size of SDGF was 32kd but not 17kd, suggesting that SDGF is not FGF itself. Northern blot analysis showed that only 6.4kb band of mRNA OF basic FGF was detected by using cDNA probe for basic FGF gene. These results suggested that SDGF is different from basic FGF. Further cloning is in progressusing the antibody with cross-reactivity with SDGF.