Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Biochemical and biophysical research communications, 2007-09, Vol.360 (4), p.772-777

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2007

Quelle

MEDLINE

Beschreibungen/Notizen

• 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)-β 1 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-β 1 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.