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Mycophenolic acid inhibits albumin-induced MCP-1 expression in renal tubular epithelial cells through the p38 MAPK pathway

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Abstract

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.

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Authors and Affiliations

  1. Department of Nephrology, Zhongnan Hospital, Wuhan University, 430071, Wuhan, Hubei, People’s Republic of China

    Hua Shui, Ping Gao & Xiaoyun Si

  2. Department of Nephrology, Renmin Hospital, Wuhan University, 430060, Wuhan, Hubei, People’s Republic of China

    Guohua Ding

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  1. Hua Shui
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  2. Ping Gao
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  3. Xiaoyun Si
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  4. Guohua Ding
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Correspondence to Hua Shui.

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Shui, H., Gao, P., Si, X. et al. Mycophenolic acid inhibits albumin-induced MCP-1 expression in renal tubular epithelial cells through the p38 MAPK pathway. Mol Biol Rep 37, 1749–1754 (2010). https://doi.org/10.1007/s11033-009-9599-y

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  • DOI: https://doi.org/10.1007/s11033-009-9599-y

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