High Glucose Induces MCP-1 Expression in Cultured Human Mesangial Cells Partly Via Tyrosine Kinase-AP-1 Pathway.
- Author:
Sang Pil CHANG
1
;
Choung Soo KIM
;
Myung Jae KIM
;
Soon Bae KIM
;
Sang Koo LEE
;
Jung Sik PARK
Author Information
1. Department of Internal Medicine,College Medicine, University of Ulsan, Korea.
- Publication Type:Original Article
- Keywords:
Glucose;
MCP-1;
AP-1;
Protein tyrosine kinase;
Mesangial cells
- MeSH:
Blotting, Northern;
Cell Culture Techniques;
Cytokines;
Diabetic Nephropathies;
Enzyme-Linked Immunosorbent Assay;
Glomerulonephritis;
Glucose*;
Humans*;
Intercellular Signaling Peptides and Proteins;
Mannitol;
Mesangial Cells*;
Monocytes;
NF-kappa B;
Protein-Tyrosine Kinases;
RNA, Messenger;
Sensitivity and Specificity;
Signal Transduction;
Transcription Factor AP-1;
Tyrosine*
- From:Korean Journal of Nephrology
2001;20(4):613-623
- CountryRepublic of Korea
- Language:Korean
-
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 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.
