title: Platelet-derived growth factor induces Rad expression through Egr-1 in vascular smooth muscle cells.
abstract: BACKGROUND
  Ras associated with diabetes (Rad) inhibits vascular lesion formation by reducing the attachment and migration of vascular smooth muscle cells (VSMCs). However, the transcriptional regulation of Rad in VSMCs is unclear.
  
  
  RESULTS
  We found that Platelet-Derived Growth Factor (PDGF)induced Rad expression in a time- and dose-dependent manner in rat aortic smooth muscle cells (RASMCs) using quantitative real-time PCR. By serial deletion analysis of the Rad promoter, we identified that two GC-rich early growth response-1 (Egr-1) binding sites are essential for PDGF-induced Rad promoter activation. Overexpression of Egr-1 in RASMCs strongly stimulated Rad expression while the Egr-1 corepressor, NGFI-A binding protein 2 (NAB2), repressed PDGF-induced Rad up-regulation in a dose-dependent manner. Direct binding of Egr-1 to the Rad promoter region was further confirmed by chromatin immunoprecipitation assays.
  
  
  CONCLUSIONS
  Our results demonstrate that Rad is regulated by PDGF through the transcriptional factor Egr-1 in RASMCs.
authors.affiliation: The Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
authors.forename: Meiling
authors.initials: M
authors.lastname: Zhang
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
authors.forename: Jifeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Chunlei
authors.initials: C
authors.lastname: Chen
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Chen
authors.forename: Jing-Wei
authors.initials: JW
authors.lastname: Xiong
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000166:cytology; D001665:Binding Sites; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D005786:Gene Expression Regulation; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D016297:Mutagenesis, Site-Directed; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D010957:Plasmids / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D051766:Early Growth Response Protein 1; D010982:Platelet-Derived Growth Factor; C490031:Rrad protein, rat; D018631:ras Proteins