TY - JOUR
T1 - Effects of anti-TGF-β type II receptor antibody on experimental glomerulonephritis
AU - Kasuga, Hirotake
AU - Ito, Yasuhiko
AU - Sakamoto, Shinji
AU - Kawachi, Hiroshi
AU - Shimizu, Fujio
AU - Yuzawa, Yukio
AU - Matsuo, Seiichi
N1 - Funding Information:
Part of this work was supported by a grant for the year 2000 from the Aichi Kidney Foundation. We appreciate the excellent technical assistance of N. Suzuki, N. Asano, T. Katahara, and Y. Fujitani. We also thank Nigishi Hotta, M.D. (Professor and Chairman, Internal Medicine III, Nagoya University School of Medicine), and Nobuo Sakamoto, M.D. (Director, Chubu Rousai Hospital), for their useful advice and encouragement.
PY - 2001/11
Y1 - 2001/11
N2 - 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-β (TGF-β) and TGF-β type II receptor (TGF-βIIR) may play an important role in the ongoing fibrotic process. TGF-βIIR and TGF-β have been reported to be up-regulated in human glomerulopathies. In order to block the TGF-β system, many studies have inhibited TGF-β itself, but not its receptors. Our study explored the effects of fully human monoclonal antibody against TGF-βIIR (hTGF-βIIRAb) on experimental proliferative glomerulonephritis. Methods. hTGF-βIIRAb was generated from Xenomice. The expression of TGF-βIIR was studied by immunohistochemistry in normal and anti-Thy-1 nephritis rats. hTGF-βIIRAb 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-βIIRAb were assessed by histological and immunopathological measurements. Results. The specificity of hTGF-βIIRAb was confirmed by ELISA and Western blot analysis. By immunostaining, TGFβIIR expression was up-regulated in the proliferative lesions of anti-Thy-1 nephritis at day 7. In the hTGF-βIIRAb-treated group, the extent of mesangial expansion was less than that in the control group. By immunohistology, α-smooth muscle actin, fibronectin-EDA, and type I collagen were significantly reduced in the hTGF-βIIRAb-treated group. Conclusions. Anti-TGF-βIIR antibody ameliorated ECM accumulation in anti-Thy-1 nephritis. Our data suggest that TGF-βIIR may be one of the therapeutic targets, and that fully human monoclonal antibody against TGF-βIIR may have a new therapeutic potential for renal fibrosis.
AB - 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-β (TGF-β) and TGF-β type II receptor (TGF-βIIR) may play an important role in the ongoing fibrotic process. TGF-βIIR and TGF-β have been reported to be up-regulated in human glomerulopathies. In order to block the TGF-β system, many studies have inhibited TGF-β itself, but not its receptors. Our study explored the effects of fully human monoclonal antibody against TGF-βIIR (hTGF-βIIRAb) on experimental proliferative glomerulonephritis. Methods. hTGF-βIIRAb was generated from Xenomice. The expression of TGF-βIIR was studied by immunohistochemistry in normal and anti-Thy-1 nephritis rats. hTGF-βIIRAb 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-βIIRAb were assessed by histological and immunopathological measurements. Results. The specificity of hTGF-βIIRAb was confirmed by ELISA and Western blot analysis. By immunostaining, TGFβIIR expression was up-regulated in the proliferative lesions of anti-Thy-1 nephritis at day 7. In the hTGF-βIIRAb-treated group, the extent of mesangial expansion was less than that in the control group. By immunohistology, α-smooth muscle actin, fibronectin-EDA, and type I collagen were significantly reduced in the hTGF-βIIRAb-treated group. Conclusions. Anti-TGF-βIIR antibody ameliorated ECM accumulation in anti-Thy-1 nephritis. Our data suggest that TGF-βIIR may be one of the therapeutic targets, and that fully human monoclonal antibody against TGF-βIIR may have a new therapeutic potential for renal fibrosis.
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U2 - 10.1046/j.1523-1755.2001.00990.x
DO - 10.1046/j.1523-1755.2001.00990.x
M3 - Article
C2 - 11703592
AN - SCOPUS:0034783503
VL - 60
SP - 1745
EP - 1755
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 5
ER -