Effects of anti-TGF-beta type II receptor antibody on experimental glomerulonephritis

Background. Renal fibrosis, characterized by the accumulation of extracellu lar matrix (ECM), is a common histopathological feature of progressive rena l disease of diverse etiology. Interaction between transforming growth fact or-beta (TGF-beta) and TGF-beta type II receptor (TGF-beta IIR) may play an important role in the ongoing fibrotic process. TGF-beta IIR and TGF-beta have been reported to be up-regulated in human glomerulopathies. In order t o block the TGF-beta system, many studies have inhibited TGF-beta itself, b ut not its receptors. Our study explored the effects of fully human monoclo nal antibody against TGF-beta IIR (hTGF-beta IIRAb) on experimental prolife rative glomerulonephritis. Methods. hTGF-beta IIRAb was generated from Xenomice. The expression of TGF -beta IIR was studied by immunohistochemistry in normal and anti-Thy-1 neph ritis rats. hTGF-beta IIRAb 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-beta IIRAb were assessed by histological and immunopathol ogical measurements. Results. The specificity of hTGF-beta IIRAb was confirmed by ELISA and West ern blot analysis. By immunostaining, TGF-beta IIR expression was up-regula ted in the proliferative lesions of anti-Thy-1 nephritis at day 7. In the h TGF-beta IIRAb-treated group, the extent of mesangial expansion was less th an that in the control group. By immunohistology, alpha -smooth muscle acti n, fibronectin-EDA, and type I collagen were significantly reduced in the h TGF-beta IIRAb-treated group. Conclusions. Anti-TGF-beta IIR antibody ameliorated ECM accumulation in ant i-Thy-1 nephritis. Our data suggest that TGF-beta IIR may be one of the the rapeutic targets, and that fully human monoclonal antibody against TGF-beta IIR may have a new therapeutic potential for renal fibrosis.