REGULATORY MECHANISMS OF TRANSCRIPTIONAL REGULATORY FACTOR C/EBPdelta ON CELLULAR DEVELOPMENT OR HYPERTROPHY IN VASCULAR SMOOTH MUSCLE CELLS.

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C/EBPdelta is well known to be one of major members in CCAAT/enhancer-binding proteins. However, roles of C/EBPdelta on cellular development or hypertrophy in vascular smooth muscle cells (VSMC) are still unclear. In the present study, we have demonstrated that C/EBPdelta is not expressed in normal tissues, and its mRNA expression is observed in VSMC derived from genetically hypertensive rat, SHR.In addition, C/EBPdelta gene expression in VSMC is markedly induced by treatment with IL-1beta in a dose- or time- dependent manner. Structural and functional studies of the rat C/EBPdelta gene revealed that a TATA-like sequence (TAGAAAA) was located at 31-bp upstream region of the transcriptional start site, and an upstream control element (UCE) spanning -235 through -82 was essential for basic transcriptional activity of the gene. In addition, we also investigated effects of UCE on heterologous gene promoters including smooth muscle alpha-actin gene promoter and SV40 promoter. Interestingly, … More UCE specifically activated the promoter efficiency of alpha-actin gene suggesting that C/EBPdelta gene may be positively regulated by UCE via a cell- or promoter-type specific manner. Furthermore, to investigate roles of C/EBPdelta on pathological changes in the vessel wall, we performed an immunohistochemical detection of C/EBPdelta and platelet-derived growth factor alpha-receptor (PDGFalphaR), which is mainly controlled by C/EBPdelta at a transcriptional level, using damaged vessel walls after balloon injury. While a marked induction of C/EBPdelta protein was seen in smooth muscle layr or adventitia at the early phase (1-2 days after injury), PDGFalphaR protein was highly expressed in the neointima at the established phase (2-3 weeks after injury). These results strongly indicate that C/EBPdelta is functionally involved in the cellular development or hypertrophy in VSMC.In the future, we are planing to make C/EBPdelta-transgenic rats, and they are supposed to be good models to know a new function of C/EBPdelta in vivo. Less