title: DJ-1/park7 protects against neointimal formation via the inhibition of vascular smooth muscle cell growth.
abstract: OBJECTIVE
  DJ-1/park7 is a ubiquitously expressed multifunctional protein that plays essential roles in a variety of cells. However, its function in the vascular system has not been determined. We investigated the protective roles of DJ-1/park7 in vascular disorders, especially in neointimal hyperplasia.
  
  
  RESULTS
  DJ-1/park7 was strongly expressed in the neointimal layer, in which its oxidized form was predominant. Treatment of vascular smooth muscle cells (VSMCs) from the mouse aorta with H(2)O(2) increased the oxidation of DJ-1/park7 visualized on two-dimensional electrophoresis gels. The growth of VSMCs in FBS-containing media and the release of H(2)O(2) were significantly increased in DJ-1/park7(-/-) knockout mice compared with DJ-1/park7(+/+) wild-type mice. The expression of cyclin D1 and the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 were greater in VSMCs from the DJ-1/park7(-/-) aorta than from the DJ-1/park7(+/+) aorta. Both of these measures were inhibited by treatment with an ERK1/2 inhibitor or antioxidants and in DJ-1/park7-overexpressing cells. VSMC proliferation, cyclin D1 expression, and ERK1/2 phosphorylation in response to platelet-derived growth factor-BB were upregulated in DJ-1/park7(-/-) compared with DJ-1/park7(+/+) mice. VSMCs of DJ-1/park7(-/-) mice exhibited higher levels of sprout outgrowth of aortic strips and neointimal plaque formation elicited by carotid artery ligation compared with those of DJ-1/park7(+/+) mice.
  
  
  CONCLUSIONS
  These results indicate that DJ-1/park7 is involved in the growth of VSMCs, thereby inhibiting neointimal hyperplasia, and suggest that it might play protective roles in vascular remodelling.
authors.affiliation: Department of Medicine,  Institute of Functional Genomics, School of Medicine, Konkuk University, 322 Danwol-dong, Chungju 380-701,  Korea.
authors.forename: Kyung Jong
authors.initials: KJ
authors.lastname: Won
authors.forename: Seung Hyo
authors.initials: SH
authors.lastname: Jung
authors.forename: Chang-Kwon
authors.initials: CK
authors.lastname: Lee
authors.forename: Hae Rang
authors.initials: HR
authors.lastname: Na
authors.forename: Kang Pa
authors.initials: KP
authors.lastname: Lee
authors.forename: Dong-Youb
authors.initials: DY
authors.lastname: Lee
authors.forename: Eun-Seok
authors.initials: ES
authors.lastname: Park
authors.forename: Wahn Soo
authors.initials: WS
authors.lastname: Choi
authors.forename: Sun Bo
authors.initials: SB
authors.lastname: Shim
authors.forename: Bokyung
authors.initials: B
authors.lastname: Kim
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000503:physiopathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000503:physiopathology; D058426:Neointima / Q000503:physiopathology* / Q000517:prevention & control*; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D015513:Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D054464:Peroxiredoxins; D010766:Phosphorylation / Q000187:drug effects; D000071617:Protein Deglycase DJ-1; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D015513:Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D017382:Reactive Oxygen Species; D019938:Cyclin D1; D054464:Peroxiredoxins; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1