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

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

Research output: Contribution to journalArticlepeer-review

122 Citations (Scopus)

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)-β1 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-β1 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.

Original languageEnglish
Pages (from-to)772-777
Number of pages6
JournalBiochemical and biophysical research communications
Volume360
Issue number4
DOIs
Publication statusPublished - 2007 Sep 7

Keywords

  • CCR2
  • Diabetic nephropathy
  • Glomerulosclerosis
  • Macrophage
  • Propagermanium

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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