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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 
Citation
 AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, Vol.295(3) : 749-757, 2008 
Journal Title
 AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 
ISSN
 1931-857X 
Issue Date
2008
MeSH
Animals ; Cells, Cultured ; Chemokine CCL2/genetics ; Chemokine CCL2/metabolism* ; Collagen Type IV/metabolism* ; Diabetic Nephropathies/metabolism ; Fibronectins/metabolism* ; Glucose/metabolism ; Humans ; Mesangial Cells/metabolism* ; Mice ; Mice, Transgenic ; Mutation ; RNA, Small Interfering/genetics ; Receptors, CCR2/genetics ; Receptors, CCR2/metabolism* ; Transfection ; Transforming Growth Factor beta1/metabolism
Keywords
diabetic nephropathy ; monocyte chemoattractant protein-1 ; transforming growth factor-β1 ; extracellular matrix
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.
Files in This Item:
T200800731.pdf Download
DOI
10.1152/ajprenal.00547.2007
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kang, Shin Wook(강신욱) ORCID logo https://orcid.org/0000-0002-5677-4756
Kim, Kun Hong(김건홍) ORCID logo https://orcid.org/0000-0001-5639-6372
Kim, Dong Ki(김동기)
Moon, Sung Jin(문성진)
Yoo, Tae Hyun(유태현) ORCID logo https://orcid.org/0000-0002-9183-4507
Lee, Jung Eun(이정은) ORCID logo https://orcid.org/0000-0003-0917-2872
Han, Dae Suk(한대석)
Han, Seung Hyeok(한승혁) ORCID logo https://orcid.org/0000-0001-7923-5635
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/106989
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