TJN-331 Improves Anti-glomerular Basement Membrane Nephritis by Inhibiting the Production of Intraglomerular Transforming Growth Factor-β1
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概要
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Transforming growth factor-β1 (TGF-β1) plays an important role in the development of glomerulonephritis. The study of experimental glomerulonephritis in rats was performed to examine the antinephritic effects of TJN-331, a new herbally-derived chemical compound. To clarify the action of TJN-331 ((E)-N-(3,4-dimethoxyphenethyl)-N-methyl-3-(3-pyridyl)-2-propenamide) on TGF-β1 production, glomeruli were isolated from rats with antiglomerular basement membrane (GBM) nephritis and incubated for 48 h with test drugs in vitro. Next, we examined the effects of TJN-331 on rat anti-GBM nephritis induced by injection with anti-GBM serum. TJN-331 dose-dependently inhibited the increase in total and mature TGF-β1 production from nephritic glomeruli, although it did not inhibit TGF-β1 production from normal glomeruli. Administration of TJN-331, at a dose of 2 mg/kg/d, per os (p.o.), prevented proteinuria and increased crescent formation and adhesion of capillary walls to Bowmans capsule. The increases in mature TGF-β1 protein production and TGF-β1 staining score in nephritic rats were reversed by TJN-331 treatment. These results suggest that TJN-331 inhibits proteinuria and histopathological changes in glomeruli via suppression of TGF-β1 production from inflamed glomeruli.
著者
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TAKEDA Hiroshi
Department of Medical Information Science, Osaka University Graduate School of Medicine
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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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Saegusa Yayoi
Tsumura Research Laboratories, Tsumura & Co.
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Sadakane Chiharu
Tsumura Research Laboratories, Tsumura & Co.
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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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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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Sadakane Chiharu
Tsumura Central Research Laboratory 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 Research Laboratories, Tsumura & Co.
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Shindo Shoichiro
Tsumura & Co., Tsumura Research Laboratories
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Koseki Junichi
Tsumura Research Laboratories, Tsumura & Co.
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Saegusa Yayoi
Tsumura Research Laboratories, Tsumura & Co.
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Takeda Shuichi
Tsumura Research Laboratories, Tsumura & Co.
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Hattori Tomohisa
Tsumura Research Laboratories, Tsumura & Co.
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Sadakane Chiharu
Tsumura Research Laboratories, Tsumura & Co.
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Koseki Junichi
Tsumura & Co., Tsumura Research Laboratories
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Sadakane Chiharu
Tsumura & Co., Tsumura Research Laboratories
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