Literature DB >> 17631861

Inhibition of MCP-1/CCR2 pathway ameliorates the development of diabetic nephropathy.

Hiroshi Kanamori1, Takeshi Matsubara, Akira Mima, Eriko Sumi, Kojiro Nagai, Toshikazu Takahashi, Hideharu Abe, Noriyuki Iehara, Atsushi Fukatsu, Hiroshi Okamoto, Toru Kita, Toshio Doi, Hidenori Arai.   

Abstract

Monocyte chemoattractant protein (MCP-1) is an important mediator for macrophage recruitment in atherosclerosis and various glomerulonephritis. However, the role of MCP-1 and its receptor CCR2 in the progression of diabetic nephropathy remains unknown. Using a type 1 diabetic nephropathy model that shows noticeable glomerulosclerosis, we examined the role of MCP-1/CCR2 by propagermanium (Pro; CCR2 antagonist) treatment, and confirmed it by transfection of plasmids carrying the 7ND (a mutant of MCP-1) gene. We measured the mesangial matrix expansion, type IV collagen (Col4), transforming growth factor (TGF)-beta1 positive area, and macrophage infiltration in glomeruli after 12 weeks. Mesangial matrix expansion and macrophage infiltration were increased in diabetic mice and inhibited by Pro or 7ND-treatment. Increased glomerular expression of Col4 and TGF-beta1 in diabetic mice was also ameliorated. Thus blocking the MCP-1/CCR2 pathway ameliorated glomerulosclerosis, indicating that the MCP-1/CCR2 pathway plays a crucial role in the progression of diabetic nephropathy.

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Year:  2007        PMID: 17631861     DOI: 10.1016/j.bbrc.2007.06.148

Source DB:  PubMed          Journal:  Biochem Biophys Res Commun        ISSN: 0006-291X            Impact factor:   3.575


  62 in total

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