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

Cited 38 time in Web of Science Cited 41 time in Scopus
Authors
Park, Jehyun; Ryu, Dong-Ryeol; Li, Jin Ji; Jung, Dong-Sub; Kwak, Seung-Jae; Lee, Sun Ha; Yoo, Tae-Hyun; Han, Seung Hyeok; Lee, Jung Eun; Kim, Dong Ki; Moon, Sung Jin; Kim, Kunhong; Han, Dae Suk; Kang, Shin-Wook
Issue Date
2008-06-27
Publisher
American Physiological Society
Citation
Am J Physiol Renal Physiol. 295(3): F749-F757
Keywords
AnimalsCells, CulturedChemokine CCL2/genetics/*metabolismCollagen Type IV/*metabolismDiabetic Nephropathies/metabolismFibronectins/*metabolismGlucose/metabolismHumansMesangial Cells/*metabolismMiceMice, TransgenicMutationRNA, Small Interfering/geneticsReceptors, CCR2/genetics/*metabolismTransfectionTransforming Growth Factor beta1/metabolism
Abstract
Monocyte chemoattractant protein-1 (MCP-1) 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 pathogenesis 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)-beta1, MCs were also treated with TGF-beta1 (2 ng/ml) with or without mMCP-1 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-beta1 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-beta1 levels were significantly attenuated by mMCP-1, CCR2 siRNA, and RS102895 (P < 0.05). MCP-1 directly increased ECM protein expression, and this increase was inhibited by an anti-TGF-beta1 antibody. In addition, TGF-beta1-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-beta1 may contribute to ECM accumulation in DN.
ISSN
0363-6127 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18579703

http://ajprenal.physiology.org/cgi/reprint/295/3/F749.pdf

http://hdl.handle.net/10371/68261
DOI
https://doi.org/10.1152/ajprenal.00547.2007
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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