Effect of TJN-331 on Anti-Thy1 Nephritis in Rats via Inhibition of Transforming Growth Factor-β1 Production
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概要
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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.
- 公益社団法人 日本薬学会の論文
著者
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TAKEDA Hiroshi
Department of Medical Information Science, Osaka University Graduate School of Medicine
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KASE Yoshio
Tsumura Research Laboratories, Tsumura & Co.
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HATTORI Tomohisa
Tsumura and Co., Pharmacology Research Department, R&D Division
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TAKEDA Shuichi
Tsumura and Co., Pharmacology Research Department, R&D Division
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Hattori Tomohisa
Tsumura & Co. Tsumura Res. Laboratories
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Koseki Junichi
Tsumura Research Laboratories, Tsumura & Co.
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Hasegawa Yoshihiro
Tsumura Research Laboratories, Tsumura & Co.
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Shindo Shoichiro
Tsumura Research Laboratories, Tsumura & Co.
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Maruyama Hirobumi
Iwaki Meisei University
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Takeda Hiroshi
Department Of Earth And Planetary Science The University Of Tokyo
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Kase Yoshio
Tsumura Research Institute Medicinal Evaluation Laboratory
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Saegusa Yayoi
Department of Pathophysiology and Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutica
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Sadakane Chiharu
Department of Pathophysiology and Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutica
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Sadakane Chiharu
Tsumura Research Laboratories Tsumura & Co.
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Hasegawa Yoshihiro
Tsumura Research Laboratories Tsumura & Co.
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Koseki Junichi
Tsumura Research Laboratories Tsumura & Co.
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Shindo Shoichiro
Tsumura Research Laboratories Tsumura & Co.
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Takeda Hiroshi
Department Of Abdominal Surgery Tenri Hospital
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Takeda Shuichi
Tsumura & Co. Tsumura Research Laboratories
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Hasegawa Yoshihiro
Tsumura & Co., Tsumura Research Laboratories
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Shindo Shoichiro
Tsumura & Co., Tsumura Research Laboratories
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Saegusa Yayoi
Department of Pathophysiology and Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University
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Sadakane Chiharu
Department of Pathophysiology and Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University
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Koseki Junichi
Tsumura & Co., Tsumura Research Laboratories
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Kase Yoshio
Tsumura & Co., Tsumura Research Laboratories
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