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Characterization of hepatic fibroblasts in the development of NASH using a novel mouse model.

Research Project

Project/Area Number 16K19331
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Gastroenterology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

SAKAI Takeru  東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (20727078)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords肝線維化 / 線維芽細胞 / 体重減少 / 糖尿病 / 内科 / 肥満 / 非アルコール性脂肪性肝炎
Outline of Final Research Achievements

To elucidate the pathophysiological changes of hepatic fibroblasts in the development of non-alcoholic steatohepatitis (NASH), collagen promoter-driven GFP transgenic mice were crossed with Melanocortin 4 receptor-deficient (MC4R-KO) mice. Transcriptome analysis was performed using fibroblasts separated from NASH livers of Western diet-fed Collagen-GFP transgenic MC4R-KO mice. Expression of genes related to extracellular matrix organization, cell adhesion, and wound healing was increased in fibroblasts from NASH livers compared to quiescent hepatic stellate cells, suggesting these data represents the characteristics of activated fibroblasts. Collagen-GFP transgenic MC4R-KO mice would be a useful model to investigate the functional changes of hepatic fibroblasts in the development and resolution process of NASH.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (5 results)

All 2017 2016 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results) Remarks (1 results)

  • [Journal Article] CD11c+ resident macrophages drive hepatocyte death-triggered liver fibrosis in a murine model of nonalcoholic steatohepatitis2017

    • Author(s)
      Itoh Michiko、Suganami Takayoshi、Kato Hideaki、Kanai Sayaka、Shirakawa Ibuki、Sakai Takeru、Goto Toshihiro、Asakawa Masahiro、Hidaka Isao、Sakugawa Hiroshi、Ohnishi Koji、Komohara Yoshihiro、Asano Kenichi、Sakaida Isao、Tanaka Masato、Ogawa Yoshihiro
    • Journal Title

      JCI Insight

      Volume: 2 Issue: 22 Pages: 1-16

    • DOI

      10.1172/jci.insight.92902

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] NASH発症過程におけるマクロファージの形質変化-hepatic crown-like structureに注目して-2017

    • Author(s)
      伊藤美智子、菅波孝祥、金井紗綾香、白川伊吹、酒井健、後藤俊宏、浅川雅博、日高勲、坂井田功、小川佳宏
    • Organizer
      第38回日本肥満学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Hepatocyte death-triggered CD11c-positive macrophage accumulation induces liver fibrosis in a murine model of non-alcoholic steatohepatitis.2017

    • Author(s)
      Michiko Itoh, Takayoshi Suganami, Sayaka Kanai, Ibuki Shirakawa, Takeru Sakai, Toshihiro Goto, Masahiro Asakawa, Isao Hidaka, Isao Sakaida, Yoshihiro Ogawa
    • Organizer
      AASLD The Liver Meeting 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] NASH動物モデルに対する減量介入が肝病変に及ぼす効果の検討2016

    • Author(s)
      酒井建、伊藤美智子、後藤俊宏、浅川雅博、白川伊吹、金井紗綾香、菅波孝祥、小川佳宏
    • Organizer
      第37回日本肥満学会
    • Place of Presentation
      東京ファッションタウンビル(東京都江東区)
    • Year and Date
      2016-10-07
    • Related Report
      2016 Research-status Report
  • [Remarks] 東京医科歯科大学大学院医歯学総合研究科 分子内分泌代謝学分野

    • URL

      http://www.tmd.ac.jp/grad/cme/index.html

    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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