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

Hirotake Kasuga, Yasuhiko Ito, Shinji Sakamoto, Hiroshi Kawachi, Fujio Shimizu, Yukio Yuzawa, Seiichi Matsuo

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)1745-1755
Number of pages11
JournalKidney International
Volume60
Issue number5
DOIs
Publication statusPublished - 01-01-2001
Externally publishedYes

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Growth Factor Receptors
Transforming Growth Factors
Glomerulonephritis
Antibodies
Nephritis
Kidney
Extracellular Matrix
Fibrosis
Monoclonal Antibodies
Collagen Type I
Fibronectins
Smooth Muscle
Actins
Western Blotting
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Kasuga, Hirotake ; Ito, Yasuhiko ; Sakamoto, Shinji ; Kawachi, Hiroshi ; Shimizu, Fujio ; Yuzawa, Yukio ; Matsuo, Seiichi. / Effects of anti-TGF-β type II receptor antibody on experimental glomerulonephritis. In: Kidney International. 2001 ; Vol. 60, No. 5. pp. 1745-1755.
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abstract = "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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Kasuga, H, Ito, Y, Sakamoto, S, Kawachi, H, Shimizu, F, Yuzawa, Y & Matsuo, S 2001, 'Effects of anti-TGF-β type II receptor antibody on experimental glomerulonephritis', Kidney International, vol. 60, no. 5, pp. 1745-1755. https://doi.org/10.1046/j.1523-1755.2001.00990.x

Effects of anti-TGF-β type II receptor antibody on experimental glomerulonephritis. / Kasuga, Hirotake; Ito, Yasuhiko; Sakamoto, Shinji; Kawachi, Hiroshi; Shimizu, Fujio; Yuzawa, Yukio; Matsuo, Seiichi.

In: Kidney International, Vol. 60, No. 5, 01.01.2001, p. 1745-1755.

Research output: Contribution to journalArticle

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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

PY - 2001/1/1

Y1 - 2001/1/1

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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