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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doaj-8cf93caaf01f44b0899c00634a12e7322020-11-25T01:22:40ZengElsevierJournal of Pharmacological Sciences1347-86132011-01-011152164175Protein Tyrosine Phosphatase SHP-2 Is Positively Involved in Platelet-Derived Growth Factor–Signaling in Vascular Neointima Formation via the Reactive Oxygen Species–Related PathwayKyung-Jong Won0Hwan Myung Lee1Chang-Kwon Lee2Hai Yue Lin3Haerang Na4Ki Won Lim5Hui Yul Roh6Seobo Sim7Hyuk Song8Wahn Soo Choi9Seung Hyun Lee10Bokyung Kim11Institute of Functional Genomics, School of Medicine, Konkuk University, 322 Danwol-dong, Choongju 380-701, KoreaDepartment of Cosmetic Science, College of Natural Sciences, Hoseo University, Asan 336-795, KoreaInstitute of Functional Genomics, School of Medicine, Konkuk University, 322 Danwol-dong, Choongju 380-701, KoreaInstitute of Functional Genomics, School of Medicine, Konkuk University, 322 Danwol-dong, Choongju 380-701, KoreaInstitute of Functional Genomics, School of Medicine, Konkuk University, 322 Danwol-dong, Choongju 380-701, KoreaInstitute of Functional Genomics, School of Medicine, Konkuk University, 322 Danwol-dong, Choongju 380-701, KoreaInstitute of Functional Genomics, School of Medicine, Konkuk University, 322 Danwol-dong, Choongju 380-701, KoreaInstitute of Functional Genomics, School of Medicine, Konkuk University, 322 Danwol-dong, Choongju 380-701, KoreaInstitute of Functional Genomics, School of Medicine, Konkuk University, 322 Danwol-dong, Choongju 380-701, KoreaInstitute of Functional Genomics, School of Medicine, Konkuk University, 322 Danwol-dong, Choongju 380-701, KoreaInstitute of Functional Genomics, School of Medicine, Konkuk University, 322 Danwol-dong, Choongju 380-701, KoreaInstitute of Functional Genomics, School of Medicine, Konkuk University, 322 Danwol-dong, Choongju 380-701, Korea; Corresponding author. bkkim2@kku.ac.kr Published online in J-STAGEThe 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, migrationhttp://www.sciencedirect.com/science/article/pii/S1347861319307820 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 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 Journal of Pharmacological Sciences |
author_facet |
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 |
author_sort |
Kyung-Jong Won |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
Elsevier |
series |
Journal of Pharmacological Sciences |
issn |
1347-8613 |
publishDate |
2011-01-01 |
description |
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 |
url |
http://www.sciencedirect.com/science/article/pii/S1347861319307820 |
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