title: Inhibition of MCP-1/CCR2 pathway ameliorates the development of diabetic nephropathy.
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.
authors.affiliation: Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kanamori
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsubara
authors.forename: Akira
authors.initials: A
authors.lastname: Mima
authors.forename: Eriko
authors.initials: E
authors.lastname: Sumi
authors.forename: Kojiro
authors.initials: K
authors.lastname: Nagai
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Takahashi
authors.forename: Hideharu
authors.initials: H
authors.lastname: Abe
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Iehara
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fukatsu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okamoto
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
authors.forename: Toshio
authors.initials: T
authors.lastname: Doi
authors.forename: Hidenori
authors.initials: H
authors.lastname: Arai
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000502:physiology; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D005857:Germanium; D051379:Mice; D008813:Mice, Inbred ICR; D009942:Organometallic Compounds / Q000494:pharmacology; D011422:Propionates; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000235:genetics; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D009942:Organometallic Compounds; D011422:Propionates; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D053773:Transforming Growth Factor beta1; D005857:Germanium; C066750:propagermanium