title: Renoprotective effect of epoetin beta pegol by the prevention of M2 macrophage recruitment in Thy-1 rats.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Thy-1-GN was induced in F344 rats by injection of anti-Thy1.1 antibody. CERA (25 µg/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.
  
  
  RESULTS
  In Thy-1-GN rats, CERA suppressed increased urinary total protein, urea nitrogen, and N-acetyl-β-(D)-glucosaminidase. CERA significantly prevented glomerulosclerosis and expression of α-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.
  
  
  CONCLUSIONS
  These results suggest that CERA has potential to protect kidney function through the prevention of glomerulosclerosis, accompanied by prevention of M2 macrophage recruitment.
authors.affiliation: Product Research Department, Chugai Pharmaceutical Co., Ltd, 1-135 Komakado, Gotemba, Shizuoka, 412-8513, Japan, aizawa.ken85@chugai-pharm.co.jp.
authors.forename: Ken
authors.initials: K
authors.lastname: Aizawa
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Tashiro
authors.forename: Michinori
authors.initials: M
authors.lastname: Hirata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takeda
authors.forename: Ryohei
authors.initials: R
authors.lastname: Kawasaki
authors.forename: Koichi
authors.initials: K
authors.lastname: Endo
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine; D000199:Actins / Q000032:analysis; D000818:Animals; D001119:Arginase / Q000235:genetics; D001806:Blood Urea Nitrogen; D002465:Cell Movement / Q000187:drug effects*; D018932:Chemokine CCL2 / Q000235:genetics; D024042:Collagen Type I / Q000235:genetics; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000627:therapeutic use*; D005353:Fibronectins / Q000235:genetics; D005921:Glomerulonephritis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000517:prevention & control; D007518:Isoantibodies; D019394:Ki-67 Antigen / Q000032:analysis; D008264:Macrophages / Q000502:physiology*; D008297:Male; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011507:Proteinuria / Q000517:prevention & control; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D011916:Rats, Inbred F344; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D000118:Acetylglucosaminidase; D000199:Actins; D001119:Arginase; D018932:Chemokine CCL2; D024042:Collagen Type I; D004921:Erythropoietin; D005353:Fibronectins; D007518:Isoantibodies; D019394:Ki-67 Antigen; D011092:Polyethylene Glycols; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C491766:Ccl2 protein, rat; C035678:anti-Thy antibody; C508420:continuous erythropoietin receptor activator; C498862:Acta2 protein, rat; C542908:arginase I, rat