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

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-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 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-beta IIR (hTGF-beta IIRAb) on experimental proliferative 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 nephritis 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 immunopathological measurements. Results. The specificity of hTGF-beta IIRAb was confirmed by ELISA and Western blot analysis. By immunostaining, TGF-beta IIR expression was up-regulated in the proliferative lesions of anti-Thy-1 nephritis at day 7. In the hTGF-beta IIRAb-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-beta IIRAb-treated group. Conclusions. Anti-TGF-beta IIR antibody ameliorated ECM accumulation in anti-Thy-1 nephritis. Our data suggest that TGF-beta IIR may be one of the therapeutic targets, and that fully human monoclonal antibody against TGF-beta IIR may have a new therapeutic potential for renal fibrosis.