Vascular Smooth Muscle-Specific Transcriptional Regulation of the Gene for Platelet-Derived growth Factorβ-Receptor.

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Platelet-derived growth factor (PDGF) and its receptors are widely expressed in several tissues in the stage of cellular growth and development. In adulthood, PDGF β-receptor (PDGF βR) is mainly detected in pathological conditions such as atherosclerotic lesion and injured vascular wall. The purpose of the present study was to elucidate the underlying mechanism of PDGF βR gene expression under the pathologic conditions in vascular smooth muscle cells (VSMC), and to identify the important cis-elements responsible for the tissue-specific gene transcription. Gel mobility shift assay and supershift assay indicated that the CCAAT motif located at -67 (C67) was mainly interacted with NF-YC, and this element drove the basal promoter activity of the gene as a putative promoter. On the other hand, another important sequence essential for the basal transcription was found at a 30-bp region (R30) spanning -150 to -121. To test whether R30 actually regulates the tissue-specific transcription of PDGF βR gene, electromobility shift pattern was compared between VSMC and hepatoma cell line (HTC). We obtained the result that DNA-protein complex seen only in nuclear extracts from HTC suppressed the promoter activity in HTC in a tissue-specific manner. Furthermore, cis-element decoy transfection experiments for C67 and R30 also revealed that both elements were functionally important in mRNA expression of PDGF βR in VSMC.From these results, we concluded that the basal activity of PDGF βR gene expression was transactivated by the interaction or coordination of both C67 and R30, and the latter one mainly controlled the tissue-specific gene expression in VSMC.