title: Effects of anti-TGF-beta type II receptor antibody on experimental glomerulonephritis.
abstract: BACKGROUND
  Renal fibrosis, characterized by the accumulation of extracellular matrix (ECM), is a common histopathological feature of progressive renal disease of diverse etiology. Interaction between transforming growth factor-beta (TGF-beta) and TGF-beta type II receptor (TGF-betaIIR) may play an important role in the ongoing fibrotic process. TGF-betaIIR and TGF-beta have been reported to be up-regulated in human glomerulopathies. In order to block the TGF-beta system, many studies have inhibited TGF-beta itself, but not its receptors. Our study explored the effects of fully human monoclonal antibody against TGF-betaIIR (hTGF-betaIIRAb) on experimental proliferative glomerulonephritis.
  
  
  METHODS
  hTGF-betaIIRAb was generated from Xenomice. The expression of TGF-betaIIR was studied by immunohistochemistry in normal and anti-Thy-1 nephritis rats. hTGF-betaIIRAb or control Ab was injected intraperitoneally at day 0 and day 4 of anti-Thy-1 nephritis, and rats were sacrificed at day 7. Effects of hTGF-betaIIRAb were assessed by histological and immunopathological measurements.
  
  
  RESULTS
  The specificity of hTGF-betaIIRAb was confirmed by ELISA and Western blot analysis. By immunostaining, TGF-betaIIR expression was up-regulated in the proliferative lesions of anti-Thy-1 nephritis at day 7. In the hTGF-betaIIRAb-treated group, the extent of mesangial expansion was less than that in the control group. By immunohistology, alpha-smooth muscle actin, fibronectin-EDA, and type I collagen were significantly reduced in the hTGF-betaIIRAb-treated group.
  
  
  CONCLUSIONS
  Anti-TGF-betaIIR antibody ameliorated ECM accumulation in anti-Thy-1 nephritis. Our data suggest that TGF-betaIIR may be one of the therapeutic targets, and that fully human monoclonal antibody against TGF-betaIIR may have a new therapeutic potential for renal fibrosis.
authors.affiliation: Division of Nephrology, Internal Medicine III, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Aichi, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kasuga
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
authors.forename: S
authors.initials: S
authors.lastname: Sakamoto
authors.forename: H
authors.initials: H
authors.lastname: Kawachi
authors.forename: F
authors.initials: F
authors.lastname: Shimizu
authors.forename: Y
authors.initials: Y
authors.lastname: Yuzawa
authors.forename: S
authors.initials: S
authors.lastname: Matsuo
mesh_terms: D000199:Actins / Q000032:analysis; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D005921:Glomerulonephritis / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007678:Kidney Glomerulus / Q000473:pathology; D051379:Mice; D017346:Protein Serine-Threonine Kinases; D011507:Proteinuria / Q000628:therapy; D051381:Rats; D017208:Rats, Wistar; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis / Q000037:antagonists & inhibitors*
chemical_list: D000199:Actins; D000911:Antibodies, Monoclonal; D016326:Extracellular Matrix Proteins; D018125:Receptors, Transforming Growth Factor beta; D003404:Creatinine; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II