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

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

Research output: Contribution to journalArticle

41 Citations (Scopus)

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)-β1, MCs were also treated with TGF-β1 (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-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 RS102895 (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.

Original languageEnglish
Pages (from-to)F749-F757
JournalAmerican Journal of Physiology - Renal Physiology
Volume295
Issue number3
DOIs
Publication statusPublished - 2008 Sep

All Science Journal Classification (ASJC) codes

  • Physiology
  • Urology

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