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Mycophenolic Acid가 PDGF에 의해 증식 유도된 흰쥐 혈관평활근 세포에서 NAD(P)H Oxidase, 세포내 활성산소족 및 Mitogen-activated Protein Kinases에 미치는 영향

Other Titles
 Mechanisms Involved in the Inhibitory Effects of Mycophenolic Acid on the PDGF-induced Proliferation of Vascular Smooth Muscle Cells 
 박제현  ;  하헌주  ;  김유선  ;  허규하  ;  김명수 
 Korean Journal of Nephrology (대한신장학회지), Vol.23(4) : 567-576, 2004 
Journal Title
 Korean Journal of Nephrology (대한신장학회지) 
Issue Date
Mycophenolic Acid ; Vascular smooth muscle cells ; Platelet-derived growth factor(PDGF) ; Cell proliferation
Background: Vascular smooth muscle cell (VSMC) proliferation plays an important role in the development and progression of chronic allograft vasculopathy as in atherosclerosis. We already reported that mycophenolic acid (MPA) inhibited VSMC proliferation, cellular reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPK) in human VSMCs. In this study, we examined further molecular mechanisms involved in the anti-proliferative effect of MPA in rat VSMCs. Methods: Primary rat VSMCs were stimulated with PDGF-BB 10 ng/mL in the presence or absence of MPA and various kinds of cell signaling inhibitors. Cell proliferation was assessed by [H³]- thymidine incorporation, NAD(P)H oxidase subunits mRNA expression by RT-PCR, dichlorofluorescein- sensitive cellular ROS by FACS, and the activation of PDGF receptor-β (Tyr 751), rac1, and MAPK by Western blot analysis. Results: PDGF increased cell proliferation and cellular ROS, activation of PDGF receptor-β (Tyr 751), rac1, expression of p22phox and MOX1 mRNA, ERK 1/2, and p38 MAPK, compared to control. MPA inhibited up-regulation of rac1 phosphorylation, p22phox and MOX1 mRNA expression, cellular ROS, and phosphorylation of ERK 1/2 and p38 MAPK. However, MPA did not affect PDGF receptor-β (Tyr 751) activation. Wortmannin, diphenyleniodonium (DPI), trolox, and NAC, each inhibited PDGF- induced ERK 1/2 and p38 MAPK activation. PD98059 and p38 MAPK inhibitor also inhibited PDGF-induced cell proliferation. Conclusion: These results suggest that MPA inhibits PDGF-induced VSMC proliferation through inhibiting NAD(P)H oxidase-dependent cellular ROS leading to ERK 1/2 and p38 MAPK activation.
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1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Myoung Soo(김명수) ORCID logo https://orcid.org/0000-0002-8975-8381
Kim, Yu Seun(김유선) ORCID logo https://orcid.org/0000-0002-5105-1567
Park, Je Hyun(박제현)
Huh, Kyu Ha(허규하) ORCID logo https://orcid.org/0000-0003-1364-6989
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