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.

Abstract

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 H(2)O(2) (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.

• Authors: Kyung-Jong Won, Hwan Myung Lee, Chang-Kwon Lee, Hai Yue Lin, Haerang Na, Ki Won Lim, Hui Yul Roh, Seobo Sim, Hyuk Song, Wahn Soo Choi, Seung Hyun Lee, Bokyung Kim
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 115 Issue 2 Pg. 164-75 ( 2011) ISSN: 1347-8648 [Electronic] Japan
• PMID: 21343667 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Oxidants
• Platelet-Derived Growth Factor
• Proto-Oncogene Proteins c-sis
• Reactive Oxygen Species
• Becaplermin
• Hydrogen Peroxide
• Protein Tyrosine Phosphatase, Non-Receptor Type 11

Topics

• Animals
• Aorta (cytology)
• Becaplermin
• Carotid Arteries (pathology)
• Cell Movement (drug effects)
• Hydrogen Peroxide (pharmacology)
• Male
• Muscle, Smooth, Vascular (metabolism, pathology)
• Myocytes, Smooth Muscle (metabolism, pathology)
• Neointima (physiopathology)
• Oxidants (pharmacology)
• Phosphorylation (drug effects)
• Platelet-Derived Growth Factor (pharmacology)
• Protein Tyrosine Phosphatase, Non-Receptor Type 11 (antagonists & inhibitors, metabolism)
• Proto-Oncogene Proteins c-sis
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)