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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

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 art...

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Main Authors: Kyung-Jong Won (Author), Hwan Myung Lee (Author), Chang-Kwon Lee (Author), Hai Yue Lin (Author), Haerang Na (Author), Ki Won Lim (Author), Hui Yul Roh (Author), Seobo Sim (Author), Hyuk Song (Author), Wahn Soo Choi (Author), Seung Hyun Lee (Author), Bokyung Kim (Author)
Format: Book
Published: Elsevier, 2011-01-01T00:00:00Z.
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Summary: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. Keywords:: SHP-2, reactive oxygen species (ROS), platelet-derived growth factor (PDGF)-BB, vascular remodeling, migration
Item Description:1347-8613
10.1254/jphs.10250FP

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