論文

査読有り 国際誌
2019年8月

Adipose tissue-derived stem cells prevent fibrosis in murine steatohepatitis by suppressing IL-17-mediated inflammation.

Journal of gastroenterology and hepatology
  • Masatoshi Yamato
  • Yoshio Sakai
  • Hatsune Mochida
  • Kazunori Kawaguchi
  • Masayuki Takamura
  • Soichiro Usui
  • Akihiro Seki
  • Eishiro Mizukoshi
  • Taro Yamashita
  • Tatsuya Yamashita
  • Kousuke Ishida
  • Alessandro Nasti
  • Ho Thuy Bich Tuyen
  • Takuya Komura
  • Keiko Yoshida
  • Takashi Wada
  • Masao Honda
  • Shuichi Kaneko
  • 全て表示

34
8
開始ページ
1432
終了ページ
1440
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1111/jgh.14647

BACKGROUND AND AIM: The pathological features of non-alcoholic steatohepatitis (NASH) have not been determined, so fundamental treatment has not been established. Adipose-tissue-derived stromal/stem cells (ADSCs) are beneficial for repair/regenerative therapy of impaired organs because of their immuno-modulatory capability. In this study, we assessed how liver damage progresses during the early development phase of the murine NASH model and investigated whether ADSCs are preventatively efficacious against the fibrosis progression of NASH. METHODS: C57BL/6J mice were fed with atherogenic high fat or high-fat diet 60 developing into NASH or simple steatosis. Their hepatic inflammatory cells (HICs) were analyzed by cDNA microarray. NASH mice were treated with ADSCs injected into spleen when hepatic inflammation was initially observed, and liver samples were analyzed. The effect of ADSCs on the mice hepatic stellate cell (HSC) line stimulated by recombinant IL-17 and HICs from NASH mice was analyzed. RESULTS: The gene expression features of HICs implicated as humoral cytokine mediators of lymphoid cells during NASH development, compared with a simple steatosis model. One of the featured cytokines was IL-17. The development of hepatic fibrosis was alleviated when NASH mice were treated with ADSCs as well as treated with anti-IL-17 antibody, and the frequency of IL-17-secreting HICs decreased. NASH-HICs enhanced proliferation of HSCs, in which proliferation was sensitive to IL-17 stimulation. The stimulatory effect of NASH-HICs on the activation of HSCs was attenuated by co-culture with ADSCs. CONCLUSION: ADSCs treatment prevented progression of NASH fibrosis by suppressing IL-17-mediated inflammation, which was associated with HSCs activation.

リンク情報
DOI
https://doi.org/10.1111/jgh.14647
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30828861
URL
https://onlinelibrary.wiley.com/doi/abs/10.1111/jgh.14647
URL
http://orcid.org/0000-0003-2550-2317
ID情報
  • DOI : 10.1111/jgh.14647
  • ORCIDのPut Code : 54983272
  • PubMed ID : 30828861

エクスポート
BibTeX RIS