Effect of Mycophenolic Acid on Human Vascular Smooth Muscle Cell Proliferation and Its Signal Transduction.
- Author:
Je Hyun PARK
1
;
Hun Joo HA
;
Myoung Soo KIM
;
Ji Yeon SEO
;
Hae Jin KIM
;
Ki Il PARK
;
Yu Seun KIM
Author Information
1. Department of Surgery, Yonsei University College of Medicine, Seoul, Korea. yukim@yumc.yonsei.ac.kr
- Publication Type:Original Article
- Keywords:
Mycophenolic acid;
Human vascular smooth muscle cell;
Reactive oxygen species;
Mitogen-activated protein kinase
- MeSH:
Allografts;
Blotting, Western;
Cell Proliferation*;
Culture Media, Serum-Free;
Fibroblasts;
Humans*;
Lymphocytes;
Mesangial Cells;
Muscle, Smooth, Vascular*;
Mycophenolic Acid*;
p38 Mitogen-Activated Protein Kinases;
Phosphorylation;
Platelet-Derived Growth Factor;
Protein Kinases;
Reactive Oxygen Species;
Signal Transduction*
- From:Journal of the Korean Surgical Society
2002;62(1):1-7
- CountryRepublic of Korea
- Language:Korean
-
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 [(3)]. 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 10nM 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. H]-thymidine incorporation.
