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タイトル: Tranilast, an antifibrogenic agent, ameliorates a dietary rat model of nonalcoholic steatohepatitis
著者: Uno, Masafumi
Kurita, Seiichiro
Misu, Hirofumi link image link image
Ando, Hitoshi
Ota, Tsuguhito link image link image
Matsuzawa-Nagata, Naoto
Kita, Yuki
Nabemoto, Satoko
Akahori, Hiroshi
Zen, Yoh
Nakanuma, Yasuni link image
Kaneko, Shuichi link image link image
Takamura, Toshinari link image link image
栗田, 征一郎
御簾, 博文
太田, 嗣人
長田, 直人
全, 陽
中沼, 安二
金子, 周一
篁, 俊成
発行日: 2008年 7月
出版社(者): John Wiley & Sons
雑誌名: Hepatology
ISSN: 0270-9139
巻: 48
号: 1
開始ページ: 109
終了ページ: 118
抄録: Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease and is one of the most common liver diseases in the developed world. The histological findings of NASH are characterized by hepatic steatosis, inflammation, and fibrosis. However, an optimal treatment for NASH has not been established. Tranilast, N-(3′,4′-dimedioxycinnamoyl)- anthranilic acid, is an antifibrogenic agent that inhibits the action of transforming growth factor beta (TGF-β). This drug is used clinically for fibrogenesis-associated skin disorders including hypertrophic scars and scleroderma. TGF-β plays a central role in the development of hepatic fibrosis, and tranilast may thus ameliorate the pathogenesis of NASH. We investigated the effects of tranilast using an established dietary animal model of NASH, obese diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and nondiabetic control Long-Evans Tokushima Otsuka (LETO) rats fed a methionine-deficient and choline-deficient diet. Treatment with 2% tranilast (420 mg/kg/day) for 8 weeks prevented the development of hepatic fibrosis and the activation of stellate cells, and down-regulated the expression of genes for TGF-β and TGF-β-target molecules, including α1 procollagen and plasminogen activator-1. In addition, tranilast attenuated hepatic inflammation and Kupffer cell recruitment, and down-regulated the expression of tumor necrosis factor alpha. Unexpectedly, tranilast ameliorated hepatic steatosis and up-regulated the expression of genes involved in beta-oxidation, such as peroxisome proliferator-activated receptor α and carnitine O-palmitoyltransferase-1. Most of these effects were observed in LETO rats and OLETF rats, which suggest that the action of tranilast is mediated through the insulin resistance-independent pathway. Conclusion: Our findings suggest that targeting TGF-β with tranilast represents a new mode of therapy for NASH. Copyright © 2008 by the American Association for the Study of Liver Diseases.
DOI: 10.1002/hep.22338
URI: http://hdl.handle.net/2297/11569
資料種別: Journal Article
版表示: author
出現コレクション:1. 査読済論文(医学・保健)

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