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  • 标题:TJN-331 Improves Anti-glomerular Basement Membrane Nephritis by Inhibiting the Production of Intraglomerular Transforming Growth Factor-β1
  • 本地全文:下载
  • 作者:Yayoi Saegusa ; Chiharu Sadakane ; Junichi Koseki
  • 期刊名称:Biological and Pharmaceutical Bulletin
  • 印刷版ISSN:0918-6158
  • 电子版ISSN:1347-5215
  • 出版年度:2010
  • 卷号:33
  • 期号:8
  • 页码:1349-1354
  • DOI:10.1248/bpb.33.1349
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要: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 Bowman's 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.
  • 关键词:TJN-331;glomerular basement membrane;proteinuria transforming growth factor-β
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