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.
引用
收藏
页码:395 / 401
页数:7
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