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Protein tyrosine phosphatase SHP-2 is positively involved in platelet-derived growth factor-signaling in vascular neointima formation via the reactive oxygen species-related pathway
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نویسنده
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won k.-j. ,lee h.m. ,lee c.-k. ,lin h.y. ,na h. ,lim k.w. ,roh h.y. ,sim s. ,song h. ,choi w.s. ,lee s.h. ,kim b.
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منبع
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journal of pharmacological sciences - 2011 - دوره : 115 - شماره : 2 - صفحه:164 -175
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چکیده
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The roles of src homology domain 2-containing protein tyrosine phosphatase 2 (shp-2) and its signaling in atherosclerosis have not been explored. therefore,we investigated the roles of shp-2 in the movement of rat aortic smooth muscle cells (rasmcs) and in the neointima formation of the carotid artery. platelet-derived growth factor (pdgf)-bb (1-20 ng/ml) increased the activity and phosphorylation of shp-2 and migration in rasmcs and these were suppressed by shp-2 inhibitor nsc-87877 (30 μm) and small interfering rna of shp-2. pdgf-bb increased the phosphorylations of spleen tyrosine kinase (syk) and p38 mitogen-activated protein kinase (mapk),which were recovered by inhibition of shp-2. moreover,pdgf-bb increased the levels of reactive oxygen species (ros) and ros inhibitors decreased pdgf-bb-increased migration. treatment of rasmcs with h2o2 (100 μm) increased cell migration and shp-2 phosphorylation and also enhanced the phosphorylation levels of syk and p38 mapk. oral administration of nsc-87877 (10 mg/kg) significantly suppressed neointima formation in a rat model of carotid artery injury. these results suggest that the activity of shp-2 is controlled by ros and is positively involved in the regulation of pdgf-bb-induced rasmc migration and neointima formation. © the japanese pharmacological society.
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کلیدواژه
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Migration; Platelet-derived growth factor (PDGF)-BB; Reactive oxygen species (ROS); SHP-2; Vascular remodeling
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آدرس
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institute of functional genomics,school of medicine,konkuk university,322 danwol-dong,choongju 380-701, South Korea, department of cosmetic science,college of natural sciences,hoseo university,asan 336-795, South Korea, institute of functional genomics,school of medicine,konkuk university,322 danwol-dong,choongju 380-701, South Korea, institute of functional genomics,school of medicine,konkuk university,322 danwol-dong,choongju 380-701, South Korea, institute of functional genomics,school of medicine,konkuk university,322 danwol-dong,choongju 380-701, South Korea, institute of functional genomics,school of medicine,konkuk university,322 danwol-dong,choongju 380-701, South Korea, institute of functional genomics,school of medicine,konkuk university,322 danwol-dong,choongju 380-701, South Korea, institute of functional genomics,school of medicine,konkuk university,322 danwol-dong,choongju 380-701, South Korea, institute of functional genomics,school of medicine,konkuk university,322 danwol-dong,choongju 380-701, South Korea, institute of functional genomics,school of medicine,konkuk university,322 danwol-dong,choongju 380-701, South Korea, institute of functional genomics,school of medicine,konkuk university,322 danwol-dong,choongju 380-701, South Korea, institute of functional genomics,school of medicine,konkuk university,322 danwol-dong,choongju 380-701, South Korea
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Authors
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