Inhibition of MCP-1/CCR2 pathway ameliorates the development of diabetic nephropathy.
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.
Kanamori
Hiroshi
H
Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Matsubara
Takeshi
T
Mima
Akira
A
Sumi
Eriko
E
Nagai
Kojiro
K
Takahashi
Toshikazu
T
Abe
Hideharu
H
Iehara
Noriyuki
N
Fukatsu
Atsushi
A
Okamoto
Hiroshi
H
Kita
Toru
T
Doi
Toshio
T
Arai
Hidenori
H
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
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