Targeted overexpression of CCAAT/enhancer-binding protein-delta evokes enhanced gene transcription of platelet-derived growth factor alpha-receptor in vascular smooth muscle cells

Platelet-derived growth factor (PDGF) is thought to play a significant role in various models of vascular remodeling, particularly in the early proces s of vascular diseases. Its action is mediated by its specific receptor, th e PDGF receptor. The PDGF alpha -receptor (PDGF alphaR) plays an important role in the growth and proliferation of vascular smooth muscle cells (VSMCs ), and its gene expression is thought to be regulated by several potential transcriptional nuclear factors. However, the detailed mechanisms of tissue -specific transactivation of the PDGFaR gene in VSMCs remain to be clarifie d. We have previously demonstrated that the rat PDGF alphaR gene contains a n enhancer core sequence for CCAAT/enhancer-binding proteins (C/EBPs) in it s promoter region, and we have also suggested that C/EBP-delta is the princ ipal factor involved in the induction of tissue-specific transcriptional ac tivity of the PDGFaR gene in VSMCs. To explore the definitive roles of C/EB P-delta protein on PDGFaR gene transcription in VSMCs, we developed C/EBP-d elta transgenic rats by using a chimeric fusion gene of the mouse smooth mu scle a-actin promoter and an entire coding region of rat C/EBP-delta cDNA. This report describes the first successful targeted overexpression of C/EBP -delta capable of inducing PDGFaR gene transcription and modifying cell pro liferative activity to PDGFs. Targeted overexpression of C/EBP-delta evokes high levels of PDGFaR gene expression, susceptibility to VSMC growth, and proliferation of VSMCs to PDGFs. The results obtained reveal evidence of a new role and new functional significance of C/EBP-delta on VSMC growth via the PDGFaR during the process of vascular remodeling and atherosclerosis.