共 20 条
Renoprotective effect of epoetin beta pegol by the prevention of M2 macrophage recruitment in Thy-1 rats
被引:10
作者:
Aizawa, Ken
[1
]
Tashiro, Yoshihito
[1
]
Hirata, Michinori
[1
]
Takeda, Satoshi
[1
]
Kawasaki, Ryohei
[1
]
Endo, Koichi
[1
]
机构:
[1] Chugai Pharmaceut Co Ltd, Prod Res Dept, Shizuoka 4128513, Japan
关键词:
Continuous erythropoietin receptor activator (CERA);
Epoetin beta pegol;
Erythropoietin;
Glomerulonephritis;
Macrophage;
Renoprotection;
ALTERNATIVELY ACTIVATED MACROPHAGES;
MONOCYTE CHEMOATTRACTANT PROTEIN-1;
ERYTHROPOIETIN RECEPTOR ACTIVATOR;
GLOMERULONEPHRITIS;
EXPRESSION;
DISEASE;
CELLS;
MODEL;
D O I:
10.1007/s40620-014-0099-3
中图分类号:
R5 [内科学];
R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号:
1002 ;
100201 ;
摘要:
Glomerulonephritis (GN) develops via accumulation of extracellular matrix through macrophage recruitment in glomeruli. It is unclear whether epoetin beta pegol (continuous erythropoietin receptor activator, CERA), a long-acting erythropoiesis-stimulating agent, exerts a renoprotective effect by preventing glomerulosclerosis. We examined the renoprotective effect of CERA in rats with Thy-1 glomerulonephritis (Thy-1-GN), an animal model for mesangial proliferative glomerulonephritis. Thy-1-GN was induced in F344 rats by injection of anti-Thy1.1 antibody. CERA (25 A mu g/kg) was intravenously administered 4 h before anti-Thy1.1 antibody injection. After 6 days, blood and urine was collected for biochemical analysis and kidneys harvested for analysis of histopathology and mRNA expression. In Thy-1-GN rats, CERA suppressed increased urinary total protein, urea nitrogen, and N-acetyl-beta-(d)-glucosaminidase. CERA significantly prevented glomerulosclerosis and expression of alpha-smooth muscle actin, collagen-1, and fibronectin. Increased macrophage infiltration and up-regulated monocyte chemotactic protein-1 were significantly suppressed by CERA. Furthermore, CERA also suppressed up-regulation of arginase-1, a marker of M2 macrophages. Arginase-1 expression levels strongly correlated with levels of collagen-1 and fibronectin mRNA. These results suggest that CERA has potential to protect kidney function through the prevention of glomerulosclerosis, accompanied by prevention of M2 macrophage recruitment.
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页码:395 / 401
页数:7
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