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Mycophenolic acid inhibits platelet-derived growth factor-induced reactive oxygen species and mitogen-activated protein kinase activation in rat vascular smooth muscle cells

 Jehyun Park  ;  Hunjoo Ha  ;  Yu Seun Kim  ;  Kiil Park  ;  Kyu Ha Huh  ;  Hae Jin Kim  ;  Myoung Soo Kim  ;  Jiyeon Seo 
 AMERICAN JOURNAL OF TRANSPLANTATION, Vol.4(12) : 1982-1990, 2004 
Journal Title
Issue Date
Animals ; Cell Division/drug effects ; Cells, Cultured ; Enzyme Activation/drug effects ; Guanosine/pharmacology ; Muscle, Smooth, Vascular/cytology ; Muscle, Smooth, Vascular/drug effects ; Muscle, Smooth, Vascular/physiology* ; Mycophenolic Acid/pharmacology* ; Platelet-Derived Growth Factor/pharmacology* ; Rats ; Reactive Oxygen Species/metabolism* ; Thymidine/metabolism
Mitogen‐activated protein kinases ; mycophenolic acid ; reactive oxygen species ; vascular smooth muscle cells
Vascular smooth muscle cell (VSMC) proliferation is the major pathologic feature associated with chronic allograft nephropathy, and mycophenolic acid (MPA) inhibits VSMC proliferation. Since the role of inosine monophosphate dehydrogenase (IMPDH)-dependent de novo guanosine synthesis is limited in VSMCs, we examined the effects of MPA on platelet-derived growth factor (PDGF)-induced cellular ROS and mitogen-activated protein kinases (MAPK) activation in VSMCs. Primary cultured rat VSMCs were stimulated with PDGF-BB in the presence or absence of MPA. Cell proliferation was assessed by [3H]-thymidine incorporation, ROS by flow cytometry and MAPK activation by Western blot analysis. PDGF increased cell proliferation, cellular ROS and extracellular-regulated protein kinase (ERK) 1/2 and p38 MAPK activation by 3.4-, 1.6-, 3.3- and 3.9-fold, respectively. MPA at above 1 muM inhibited PDGF-induced cellular ROS and ERK 1/2 and p38 MAPK activation, as well as proliferation. Structurally different anti-oxidants and inhibitor of ERK or p38 MAPK blocked PDGF-induced proliferation. Anti-oxidants also inhibited ERK 1/2 and p38 MAPK activation. Exogenous guanosine partially recovered the inhibitory effect of MPA on VSMC proliferation. These results suggest that MPA may inhibit PDGF-induced VSMC proliferation partially through inhibiting cellular ROS, and subsequent ERK 1/2 and p38 MAPK activation in addition to inhibiting IMPDH.
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1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 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, Ki Il(박기일)
Huh, Kyu Ha(허규하) ORCID logo https://orcid.org/0000-0003-1364-6989
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