title: Platelet-derived growth factor-BB induces matrix metalloproteinase-2 expression and rat vascular smooth muscle cell migration via ROCK and ERK/p38 MAPK pathways.
abstract: Matrix metalloproteinases (MMP) play a pivotal role in the pathogenesis of cardiovascular diseases. Their expressions are altered in response to a variety of stimuli, including growth factors, inflammatory markers, and cytokines. In this study, we demonstrated that platelet-derived growth factor-BB (PDGF-BB) induces a dose- and time-dependent increase in MMP-2 expression in rat vascular smooth muscle cells (VSMC). Treatment with either the Rho-associated protein kinase (ROCK) inhibitor Y-27632 or suppression of ROCK-1/2 by small interfering RNA technology significantly reduced the MMP-2 expression, thus suggesting that ROCK regulates such expression. Similar results were observed when VSMC were pretreated with either U0126 or SB203580, which are selective inhibitors of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase, respectively, thus suggesting that these kinases are important for the induction of MMP-2 expression by PDGF-BB. In conclusion, these results described a novel mechanism in atherosclerosis through PDGF-BB signaling in VSMC, in which MMP-2 expression is induced via extracellular signal-regulated kinases and p38 mitogen-activated protein kinase phosphorylation, as well as ROCK.
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalian Medical University, Lvshun, Dalian, 116044, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.forename: Yin-Wei
authors.initials: YW
authors.lastname: Sun
authors.forename: Hai-Shuang
authors.initials: HS
authors.lastname: Lin
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Su
authors.forename: Yan
authors.initials: Y
authors.lastname: Fang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Wei
authors.forename: Yuan-Hua
authors.initials: YH
authors.lastname: Qin
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kohama
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000577:Amides / Q000008:administration & dosage; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D000077214:Becaplermin; D002070:Butadienes / Q000008:administration & dosage; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009570:Nitriles / Q000008:administration & dosage; D020574:Proto-Oncogene Proteins c-sis / Q000008:administration & dosage / Q000378:metabolism; D011725:Pyridines / Q000008:administration & dosage; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000577:Amides; D002070:Butadienes; D007093:Imidazoles; D009570:Nitriles; D020574:Proto-Oncogene Proteins c-sis; D011725:Pyridines; C113580:U 0126; C108830:Y 27632; D000077214:Becaplermin; C578418:ROCK1 protein, rat; C580818:ROCK2 protein, rat; D054460:rho-Associated Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; C093642:SB 203580