title: Response gene to complement 32 promotes vascular lesion formation through stimulation of smooth muscle cell proliferation and migration.
abstract: OBJECTIVE
  The objectives of this study were to determine the role of response gene to complement 32 (RGC-32) in vascular lesion formation after experimental angioplasty and to explore the underlying mechanisms.
  
  
  RESULTS
  Using a rat carotid artery balloon-injury model, we documented for the first time that neointima formation was closely associated with a significantly increased expression of RGC-32 protein. Short hairpin RNA knockdown of RGC-32 via adenovirus-mediated gene delivery dramatically inhibited the lesion formation by 62% as compared with control groups 14 days after injury. Conversely, RGC-32 overexpression significantly promoted the neointima formation by 33%. Gain- and loss-of-function studies in primary culture of rat aortic smooth muscle cells (RASMCs) indicated that RGC-32 is essential for both the proliferation and migration of RASMCs. RGC-32 induced RASMC proliferation by enhancing p34(CDC2) activity. RGC-32 stimulated the migration of RASMC by inducing focal adhesion contact and stress fiber formation. These effects were caused by the enhanced rho kinase II-α activity due to RGC-32-induced downregulation of Rad GTPase.
  
  
  CONCLUSIONS
  RGC-32 plays an important role in vascular lesion formation following vascular injury. Increased RGC-32 expression in vascular injury appears to be a novel mechanism underlying the migration and proliferation of vascular smooth muscle cells. Therefore, targeting RGC-32 is a potential therapeutic strategy for the prevention of vascular remodeling in proliferative vascular diseases.
authors.affiliation: Department of Physiology and Pharmacology, University of Georgia, Athens, 30602, USA.
authors.forename: Jia-Ning
authors.initials: JN
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Shi
authors.forename: Wei-Bing
authors.initials: WB
authors.lastname: Xie
authors.forename: Xia
authors.initials: X
authors.lastname: Guo
authors.forename: Shi-You
authors.initials: SY
authors.lastname: Chen
mesh_terms: D000818:Animals; D001483:Base Sequence; D020212:Carotid Artery Injuries / Q000209:etiology / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D008297:Male; D009124:Muscle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000473:pathology* / Q000502:physiology*; D058426:Neointima / Q000473:pathology / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018631:ras Proteins / Q000235:genetics / Q000502:physiology
chemical_list: D018797:Cell Cycle Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; C486417:Rgcc protein, rat; C490031:Rrad protein, rat; D018631:ras Proteins