Effects of anti-TGF-beta type II receptor antibody on experimental glomerulonephritis.
Effects of anti-TGF-beta type II receptor antibody on experimental glomerulonephritis.
复制标题
抗TGF-β II型受体抗体对实验性肾小球肾炎的影响。
作者：
Hirotake Kasuga;Hirotake Kasuga;Hirotake Kasuga;Yasuhiko Ito;Yasuhiko Ito;Yasuhiko Ito;S. Sakamoto;S. Sakamoto;S. Sakamoto;H. Kawachi;H. Kawachi;H. Kawachi;F. Shimizu;F. Shimizu;F. Shimizu;Y. Yuzawa;Y. Yuzawa;Y. Yuzawa;Sei;Sei;Sei
背景
以细胞外基质（ECM）积聚为特征的肾纤维化是多种病因的进行性肾脏疾病的常见组织病理学特征。转化生长因子-β（TGF-β）和TGF-β II型受体（TGF-β IIR）之间的相互作用可能在正在进行的纤维化过程中发挥重要作用。已报道TGF-β 1 R和TGF-β在人肾小球病中上调。为了阻断TGF-β系统，许多研究抑制TGF-β本身，但不抑制其受体。本研究探讨了抗TGF-β Ⅱ R全人源单克隆抗体（hTGF-β IIRAb）对实验性增生性肾小球肾炎的影响。
方法
hTGF-β IIRAb由Xenomice产生。采用免疫组化方法检测正常和抗Thy-1肾炎大鼠肾组织TGF-β Ⅱ R的表达。在抗Thy-1肾炎的第0天和第4天腹膜内注射hTGF-β IIRAb或对照Ab，并在第7天处死大鼠。通过组织学和免疫病理学测量评估hTGF-β IIRAb的作用。
结果
通过ELISA和Western blot分析证实hTGF-β IIRAb的特异性。通过免疫染色，在第7天抗Thy-1肾炎的增生性病变中TGF-β IIR表达上调。在hTGF-β IIRAb治疗组中，系膜扩张的程度小于对照组。通过免疫组织学，α-平滑肌肌动蛋白，纤连蛋白-EDA，和I型胶原蛋白显着减少hTGF-β IIRAb治疗组。
结论
抗TGF-β IIR抗体可改善抗Thy-1肾炎中的ECM积聚。我们的数据表明，TGF-β Ⅱ R可能是治疗靶点之一，并且针对TGF-β Ⅱ R的全人单克隆抗体可能具有治疗肾纤维化的新潜力。
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.
DOI：
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发表时间：
1999-04
期刊：
Journal of the American Society of Nephrology : JASN
影响因子：
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作者：
W. Baricos;S. Cortez;Michael Deboisblanc;Shi Xin
通讯作者：
W. Baricos;S. Cortez;Michael Deboisblanc;Shi Xin
DOI：
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发表时间：
1986-03
期刊：
The Journal of biological chemistry
影响因子：
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作者：
R. Ignotz;J. Massagué
通讯作者：
R. Ignotz;J. Massagué
补体和补体调节蛋白在肾小球肾炎中的作用。
DOI：
10.1007/s00281-002-0116-9
发表时间：
2003
期刊：
Springer seminars in immunopathology.
影响因子：
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作者：
Quigg,RichardJ
通讯作者：
Quigg,RichardJ