Mycophenolic Acid가 배양된 사람 혈관 평활근 세포의 증식과 그에 관여하는 세포 내 신호전달계에 미치는 영향
Effect of Mycophenolic Acid on Human Vascular Smooth Muscle Cell Proliferation and Its Signal Transduction
박제현, 하헌주, 김명수, 서지연, 김혜진, 박기일, 김유선,
소속 상세정보
박제현 ( Park Je-hyun )
연세대학교 의과대학 장기이식연구소
하헌주 ( Ha Hun-Joo )
순천향대학교 현암신장연구소
김명수 ( Kim Myoung-Soo )
연세대학교 원주의과대학 외과학교실
서지연 ( Seo Ji-Yeon )
연세대학교 의과대학 외과학교실
김혜진 ( Kim Hae-Jin )
연세대학교 의과대학 외과학교실
박기일 ( Park Ki-Il )
연세대학교 의과대학 외과학교실
김유선 ( Kim Yu-Seun )
연세대학교 의과대학 외과학교실
KMID : 0371320020620010001
Abstract
Purpose : Vascular smooth muscle cells (VSMCs) migration and proliferation play important roles in chronic allograft rejection. Mycophenolic acid (MPA) inhibits the proliferation of VSMCs, glomerular mesangial cells and fibroblasts as well
as
lymphocytes. Since reactive oxygen species (ROS) and mitogen-activated protein kinase (MAPK) play important roles in the proliferation of VSMCs, the present study examined the effects of MPA on intracellular ROS generation, activation of ERK and
p38
MAPK, and the proliferation of VSMCs cultured under platelet derived growth factor (PDGF).
Methods : Human VSMCs obtained from ATCC were cultured with RPMI-1640 containing 10% fetal bovine serum. Near confluent VSMCs were incubated with serum-free media for 48 hours to arrest and synchronize the cell growth. MPA was administered
1
hour
before the addition of PDGF. 5-(and-6)-chloromethyl-2’,7’-dichlorodihydrofluorescein (DCF)-sensitive intracellular ROS was detected by FACS. Activations of ERK1/ERK2 and p38 MAPK were measured by Western blot analysis. Proliferation of VSMC was
assessed
by [3H]-thymidine incorporation. Results
PDGF administered at 10 ng/ml, which induced human VSMCs proliferation, rapidly increased intracellular ROS by 1.6-fold (P<0.05), ERK1/ERK2 activation by 2.1-fold, (P<0.05) and p38 MAPK activation by 1.9-fold (P<0.05), respectively, as compared
to
the
control. MPA 1 and 10μM effectively inhibited PDGF-induced human VSMCs proliferation. MPA also effectively inhibited PDGF-induced intracellular ROS generation as well as ERK1/ERK2 and p38 MAPK activation.
Conclusion : The present study suggests that MPA inhibits PDGF-induced human VSMCs proliferation, possibly by inhibiting intracellular ROS generation and the phosphorylation of ERK1/ERK2 and p38 MAPK.
키워드
마이코페놀산; 사람 혈관 평활근 세포; 활성산소족; Mitogen-activated protein kinase; Mycophenolic acid; Human vascular smooth muscle cell; Reactive oxygen species; Mitogen-activated protein kinase;
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