Mycophenolic acid inhibits albumin-induced MCP-1 expression in renal tubular epithelial cells through the p38 MAPK pathway.
Proteinuria is a well-established exacerbating factor in chronic kidney disease. Although the mechanisms of albumin-induced tubulointerstitial damage have been extensively studied, the influence of mycophenolic acid (MPA) on tubular epithelial cells has not been sufficiently elucidated. MPA, the active metabolite of mycophenolate mofetil, is a potent, non-competitive, and reversible inhibitor of inosine-5'-monophosphate dehydrogenase, the rate-limiting enzyme for de novo purine synthesis. Monocyte chemoattractant protein 1 (MCP-1) is a 76-amino-acid chemokine thought to be the major chemotactic factor for monocytes. MCP-1 is found in macrophage-rich areas of atherosclerotic lesions. However, the mechanisms regulating MCP-1 expression by MPA in renal tubular epithelial cells were still unclear. In this study, the inhibitory effect of MPA on MCP-1 expression by albumin-induced renal tubular epithelial cells was investigated, and the roles of p38 mitogen-activated protein kinase (p38 MAPK) pathway were explored. MPA attenuated albumin-induced expression of MCP-1 mRNA and protein. The experiment suggested that MPA actively inhibited protein of MCP-1. The inhibitory effect of MPA on MCP-1 expression was mediated by the sequential attenuation of p38 MAPK expression. These inhibitory effects were partially inhibited by SB203580, a specific inhibitor of p38 MAPK. Taken together, these results suggest that the negative modulation of MCP-1 by MPA is partly dependent on p38 MAPK pathway.
Shui
Hua
H
Department of Nephrology, Zhongnan Hospital, Wuhan University, 430071, Wuhan, Hubei, People's Republic of China. shuihua2005@yahoo.com.cn
Gao
Ping
P
Si
Xiaoyun
X
Ding
Guohua
G
D000418:Albumins / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000166:cytology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009173:Mycophenolic Acid / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000418:Albumins; D018932:Chemokine CCL2; D007093:Imidazoles; D011725:Pyridines; D012333:RNA, Messenger; D048051:p38 Mitogen-Activated Protein Kinases; D009173:Mycophenolic Acid; C093642:SB 203580