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Korean J Nephrol. 2001 Jul;20(4):613-623. Korean. Original Article.
Chang SP , Kim CS , Kim MJ , Kim SB , Lee SK , Park JS .
Department of Internal Medicine,College Medicine, University of Ulsan, Korea.
Department of Urology,College Medicine, University of Ulsan, Korea.
Department of Internal Medicine, College Medicine, Kyunghee University, Seoul, Korea.

Infiltration of circulating monocytes into glomeruli has been implicated in the pathogenesis of glomerular injury in many human and experimental forms of glomerulonephritis. Monocyte chemoattractant protein-1(MCP-1), a potent chemokine with considerable specificity for monocytes, can be up-regulated by various cytokines and growth factors in mesangial cells. Glomerular infiltration of monocytes has been reported in diabetic nephropathy as well. However, effect of high glucose on MCP-1 expression in human mesangial cells has not been known well. We investigated the effect of high glucose on MCP-1 expression and its signal transduction pathway. Human mesangial cells were conditioned with glucose(5-60 mM) or mannitol chronically for up to 5 days. Expression of MCP-1 mRNA and protein was measured by Northern blot analysis and ELISA respectively. To examine the role of transcription factor AP-1 or NF-KB, electrophoretic mobility shift assay(EMSA) was performed. Glucose induced MCP-1 mRNA expression in a time and dose dependent manner. MCP-1 protein in cell culture supernant was also increased. Equivalent concentrations of mannitol had no significant effect. EMSA revealed that glucose increased the AP-1 binding activity in a time and dose dependent manner but not NF-B. Inhibitor of AP-1, curcumin(7.5- 15 muM) dose dependently suppressed the induction of MCP-1 mRNA by high glucose. Tyrosine kinase inhibitors such as genistein(12.5-50 muM) and herbimycin A(0.1-1 muM) inhibited the high glucose-induced MCP-1 mRNA expression in a dose dependent manner and also suppressed the high glucose-induced AP-1 binding activity. In summary, high glucose induces mesangial MCP-1 expression partly via tyrosine kinase-AP-1 pathway.

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