Korean Journal of Nephrology 2001;20(4):613-623.

논평 : 사람의 혈관간세포에서 고농도의 당에 의한 Monocyte Chemoattractant Protein-1(MCP-1) 의 발현 및 신호 전달 체계에 관한 연구 (Editorial : High Glucose Induces MCP-1 Expression in Cultured Human Mesangial Cells Partly Via Tyrosine Kinase-AP-1 Pathway)

장상필(Sang Pil Chang),김청수(Choung Soo Kim),김명재(Myung Jae Kim),김순배(Soon Bae Kim),이상구(Sang Koo Lee),박정식(Jung Sik Park)

Abstract

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 pro- tein-l(MCP-l), 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 hu- man 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-κB, 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 supemant 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 pM) dose dependently suppressed the induction of MCP-1 mRNA by high glucose. Tyrosine kinase inhibitors such as genistein(12.5-50 μM) and herbimycin A(0.1-1 μM) inhibited the high glucose-induced IvlCP-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.