Effect of TJN-331 on anti-Thy1 nephritis in rats via inhibition of transforming growth factor-β1 production.

Yayoi Saegusa, Chiharu Sadakane, Junichi Koseki, Yoshihiro Hasegawa, Shoichiro Shindo, Hirobumi Maruyama, Yoshio Kase, Shuichi Takeda, Hiroshi Takeda, Tomohisa Hattori

Department of Pathophysiology and Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060–0812, Japan.

Biological & pharmaceutical bulletin 2010

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This study was performed to examine the effects of the antifibrotic agents TJN-331 and tranilast on mesangial expansion in a rat model of anti-Thy1 nephritis. We first investigated the effects of TJN-331 and tranilast on mesangial expansion induced by anti-Thy1 serum in rats, and determined the counts of glomerular cells and proliferative cell nuclear antigen (PCNA)-positive cells. The effects of TJN-331 and tranilast on production of transforming growth factor-β1 (TGF-β1) by isolated glomeruli incubated for 48 h were then examined. The TGF-β1 staining score, the number of TGF-β1-positive cells and the TGF-β1 receptor-positive area in the anti-Thy1 nephritis model were also measured using immunohistochemistry. TJN-331 administered from day 1 (the day after anti-Thy1 serum injection) blocked an increase in mesangial matrix accumulation on days 4 and 8, compared to untreated anti-Thy1 nephritic rats. TJN-331 also inhibited both the increase in the number of glomerular cells on day 8 and the decrease in this cell count on day 2 observed in untreated nephritic rats, and TJN-331 and tranilast inhibited an increase in PCNA-positive cells in the glomerular cross section on days 4 and 8. Both TJN-331 and tranilast inhibited increases in the TGF-β1 protein content from nephritic glomeruli, the TGF-β1-positive area, and the number of TGF-β1-positive cells/cross section in anti-Thy1 nephritic glomeruli. These results suggest that TJN-331 and tranilast prevent expansion of the mesangial area by suppression of TGF-β1 secretion from inflamed glomeruli.

Citation

Yayoi Saegusa, Chiharu Sadakane, Junichi Koseki, Yoshihiro Hasegawa, Shoichiro Shindo, Hirobumi Maruyama, Yoshio Kase, Shuichi Takeda, Hiroshi Takeda, Tomohisa Hattori. Effect of TJN-331 on anti-Thy1 nephritis in rats via inhibition of transforming growth factor-β1 production. Biological & pharmaceutical bulletin. 2010;33(10):1710-5