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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概要

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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.

著者

• Lee Hwan

  Department Of Orthopaedic Surgery Yonsei University College Of Medicine

• Lee Chang

  Department Of Physiology & Immunology School Of Medicine Konkuk University

• Lee Chang-kwon

  Institute Of Medical Sciences School Of Medicine Konkuk University

• Won Kyung-jong

  Department Of Physiology & Immunology School Of Medicine Konkuk University

• Won Kyung-Jong

  Institute of Functional Genomics, School of Medicine, Konkuk University, Korea

• Lin Hai

  Institute of Functional Genomics, School of Medicine, Konkuk University, Korea

• Na Haerang

  Institute of Functional Genomics, School of Medicine, Konkuk University, Korea

• Lim Ki

  Institute of Functional Genomics, School of Medicine, Konkuk University, Korea

• Roh Hui

  Institute of Functional Genomics, School of Medicine, Konkuk University, Korea

• Sim Seobo

  Institute of Functional Genomics, School of Medicine, Konkuk University, Korea

• Song Hyuk

  Institute of Functional Genomics, School of Medicine, Konkuk University, Korea

• Choi Wahn

  Institute of Functional Genomics, School of Medicine, Konkuk University, Korea

• Lee Seung

  Institute of Functional Genomics, School of Medicine, Konkuk University, Korea

• Kim Bokyung

  Institute of Functional Genomics, School of Medicine, Konkuk University, Korea

• Lee Hwan

  Department Of Artificial Organs Research Institute National Cardiovascular Center

• Won Kyung-jong

  Institute Of Functional Genomics School Of Medicine Konkuk University

• Lee Seung

  Institute Of Agriculture And Forestry University Of Tsukuba

• Na Haerang

  Institute Of Functional Genomics School Of Medicine Konkuk University

• Lin Hai

  Institute Of Functional Genomics School Of Medicine Konkuk University

• Roh Hui

  Institute Of Functional Genomics School Of Medicine Konkuk University

• Sim Seobo

  Institute Of Functional Genomics School Of Medicine Konkuk University

• Choi Wahn

  Institute Of Functional Genomics School Of Medicine Konkuk University

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