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MCP- 1/CCR2 system is involved in high glucose-induced fibronectin and type IV collagen expression in cultured mesangial cells.

MCP- 1/CCR2 system is involved in high glucose-induced fibronectin and type IV collagen expression in cultured mesangial cells.

Authors :
Jehyun Park
Dong-ryeol Ryu
Jin Ji Li
Dong-Sub Jung
Seung-Jae Kwak
Sun Ha Lee
Tae-Hyun Yoo
Seung Hyeok Han
Jung Eun Lee
Dong Ki Kim
Sung Jin Moon
Kunhong Kim
Dae Suk Han,
Shin-Wook Kang
Source :
American Journal of Physiology: Renal Physiology; Sep2008, Vol. 295, pF749-F757, 9p, 9 Graphs
Publication Year :
2008

Abstract

Monocyte chemoattractant protein-1 (MCP-l) is a potent chemokine that plays an important role in the recruitment of macrophages. Although previous studies have demonstrated the importance of MCP-1 in the pathogen- esis of diabetic nephropathy (DN) in terms of inflammation, the role of MCP-1 and its receptor (C-C chemokine receptor 2; CCR2) in extracellular matrix (ECM) accumulation under diabetic conditions has been largely unexplored. This study was undertaken to investigate the functional role of the MCP-1/CCR2 system in high glucose-induced ECM (fibronectin and type IV collagen) protein expression in cultured mesangial cells (MCs). Mouse MCs were exposed to medium containing 5.6 mM glucose (NG), NG+24.4 mM mannitol (NG+M), or 30 mM glucose (HG) with or without mutant MCP-1 (mMCP-1), CCR2 small interfering (si)RNA, or CCR2 inhibitor (RS102895). To examine the relationship between MCP-1 and transforming growth factor (TGF)-β1, MCs were also treated with TGF-β1 (2 ng/ml) with or without mMCP-l or CCR2 siRNA. Transient transfection was performed with Lipofectamine 2000 for 24 h. Cell viability was determined by an MTT assay, mouse and human MCP-1 and TGF-β1 levels by ELISA, and CCR2 and ECM protein expression by Western blotting. Transfections of mMCP-1 and CCR2 siRNA increased human MCP-1 levels and inhibited CCR2 expression, respectively. HG-induced ECM protein expression and TGF-β1 levels were significantly attenuated by mMCP-1, CCR2 siRNA, and RS 102895 (P < 0.05). MCP-1 directly increased ECM protein expression, and this increase was inhibited by an anti-TGF-β1 antibody. In addition, TGF-β1-induced ECM protein expression was significantly abrogated by the inhibition of the MCP-1/CCR2 system (P < 0.05). These results suggest that an interaction between the MCP-1/CCR2 system and TGF-β1 may contribute to ECM accumulation in DN. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
1931857X
Volume :
295
Database :
Complementary Index
Journal :
American Journal of Physiology: Renal Physiology
Publication Type :
Academic Journal
Accession number :
34389324
Full Text :
https://doi.org/10.1152/ajprenal.00547.2007