論文

査読有り
2011年7月

Malnutrition impairs interferon signaling through mTOR and FoxO pathways in patients with chronic hepatitis C

Gastroenterology
  • Masao Honda
  • Kenji Takehana
  • Akito Sakai
  • Yusuke Tagata
  • Takayoshi Shirasaki
  • Shinobu Nishitani
  • Takahiko Muramatsu
  • Tatsuya Yamashita
  • Yasunari Nakamoto
  • Eishiro Mizukoshi
  • Yoshio Sakai
  • Taro Yamashita
  • Mikiko Nakamura
  • Tetsuro Shimakami
  • Minkyung Yi
  • Stanley M. Lemon
  • Tetsuo Suzuki
  • Takaji Wakita
  • Shuichi Kaneko
  • 全て表示

141
1
開始ページ
128
終了ページ
e2
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1053/j.gastro.2011.03.051

Background &amp
Aims: Patients with advanced chronic hepatitis C (CH-C) often are malnourished, but the effects of malnutrition on interferon (IFN) signaling and response to treatment have not been determined. We assessed the importance of the nutritional state of the liver on IFN signaling and treatment response. Methods: We studied data from 168 patients with CH-C who were treated with the combination of pegylated-IFN and ribavirin. Plasma concentrations of amino acids were measured by mass spectrometry. Liver gene expression profiles were obtained from 91 patients. Huh-7 cells were used to evaluate the IFN signaling pathway, mammalian target of rapamycin complex 1 (mTORC1), and forkhead box O (FoxO). Antiviral signaling induced by branched-chain amino acids (BCAAs) was determined using the in vitro hepatitis C virus replication system. Results: Multivariate logistic regression analysis showed that Fischer's ratio was associated significantly with nonresponders, independent of interleukin-28B polymorphisms or the histologic stage of the liver. Fischer's ratio was correlated inversely with the expression of BCAA transaminase 1, and was affected by hepatic mTORC1 signaling. IFN stimulation was impaired substantially in Huh-7 cells grown in medium that was low in amino acid concentration, through repressed mTORC1 signaling, and increased Socs3 expression, which was regulated by Foxo3a. BCAA could restore impaired IFN signaling and inhibit hepatitis C virus replication under conditions of malnutrition. Conclusions: Malnutrition impaired IFN signaling by inhibiting mTORC1 and activating Socs3 signaling through Foxo3a. Increasing BCAAs to up-regulate IFN signaling might be used as a new therapeutic approach for patients with advanced CH-C. © 2011 AGA Institute.

リンク情報
DOI
https://doi.org/10.1053/j.gastro.2011.03.051
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/21458454
ID情報
  • DOI : 10.1053/j.gastro.2011.03.051
  • ISSN : 0016-5085
  • ISSN : 1528-0012
  • PubMed ID : 21458454
  • SCOPUS ID : 79959982939

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