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(E)-N-[(3,4-dimethoxyphenethyl)]-N-methyl-3-(3-pyridyl)-2-propenamide (TJN-331) inhibits mesangial expansion in experimental IgA nephropathy in ddY mice

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Abstract

Background

TJN-331 is an inhibitor of transforming growth factor β1 (TGF-β1) production that has similar structural features to the natural product acteoside. This study was performed to examine the antinephritic effects of TJN-331 in a mouse model of experimental IgA nephropathy.

Materials and methods

IgA nephropathy was induced in ddY mice by oral administration of bovine γ globulin, followed by reticuloendothelial blocking by colloidal carbon injection and heminephrectomy. Effects of TJN-331 were examined over oral administration periods from 10 to 15 weeks after the third colloidal carbon injection. Intravenous administration of a TGF-β1-neutralizing antibody was used to investigate the role of TGF-β1 in IgA nephropathy.

Results

Administration of TJN-331 or captopril prevented elevation of serum creatinine. Histopathological examination after both experimental periods showed that TJN-331 inhibited increases in the mesangial matrix index and the number of nuclei per glomerular cross-section, compared with in untreated ddY mice with IgA nephropathy. TJN-331 prevented increase in glomerular TGF-β1 staining without affecting IgA. In the in vitro study, TJN-331 prevented total TGF-β1 production from splenocytes stimulated with concanavalin A. A neutralizing antibody against TGF-β1 prevented increase in the mesangial matrix index and the number of glomerular cells per cross-sectional area.

Conclusion

These results suggest that TJN-331 is effective against IgA nephropathy in ddY mice and acts via suppression of TGF-β1 production in glomeruli.

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Acknowledgments

The authors are grateful to Mr. Obata and Miss Horiuchi for synthesis of TJN-331.

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Authors and Affiliations

  1. Division of Pharmasciences, Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University, N12 W6, Kita-ku, Sapporo, 060-0812, Japan

    Yayoi Saegusa, Chiharu Sadakane & Hiroshi Takeda

  2. Tsumura & Co., Tsumura Research Laboratories, 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, 300-1192, Japan

    Yayoi Saegusa, Chiharu Sadakane, Junichi Koseki, Yoshihiro Hasegawa, Shoichiro Shindo, Shuichi Takeda & Tomohisa Hattori

Authors
  1. Yayoi Saegusa
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  2. Chiharu Sadakane
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  3. Junichi Koseki
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  4. Yoshihiro Hasegawa
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  5. Shoichiro Shindo
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  6. Shuichi Takeda
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  7. Hiroshi Takeda
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  8. Tomohisa Hattori
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Correspondence to Tomohisa Hattori.

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Saegusa, Y., Sadakane, C., Koseki, J. et al. (E)-N-[(3,4-dimethoxyphenethyl)]-N-methyl-3-(3-pyridyl)-2-propenamide (TJN-331) inhibits mesangial expansion in experimental IgA nephropathy in ddY mice. Clin Exp Nephrol 14, 528–535 (2010). https://doi.org/10.1007/s10157-010-0338-4

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  • DOI: https://doi.org/10.1007/s10157-010-0338-4

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