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

被引：54

作者：

Kasuga, H

Ito, Y

Sakamoto, S

Kawachi, H

Shimizu, F

Yuzawa, Y

Matsuo, S

机构：

[1] Nagoya Univ, Sch Med, Div Nephrol, Showa Ku, Nagoya, Aichi 4668550, Japan

[2] Chubu Rousai Hosp, Aichi, Japan

[3] Japan Tobacco Inc, Cent Pharmaceut Res Inst, Pharmaceut Frontier Res Labs, Kanagawa, Japan

[4] Niigata Univ, Sch Med, Inst Nephrol, Dept Cell Biol, Niigata, Japan

来源：

KIDNEY INTERNATIONAL | 2001年 / 60卷 / 05期

关键词：

human monoclonal antibody; fibronectin-EDA; renal fibrosis; extracellular matrix; proliferative glomerular nephritis; scarring;

D O I：

10.1046/j.1523-1755.2001.00990.x

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：1745 / 1755

页数：11

共 38 条

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