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The development of hepatic fibrosis suppression focusing on hepatic stellate cell energy metabolism

Research Project

Project/Area Number 17K15949
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Gastroenterology
Research InstitutionYamaguchi University

Principal Investigator

IWAMOTO Takuya  山口大学, 大学院医学系研究科, 助教 (80634716)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords肝星細胞 / 肝硬変 / 骨髄細胞 / αSMA / 線維化 / 間葉系幹細胞 / 肝線維化 / 肝硬変症
Outline of Final Research Achievements

We studied the activation of hepatic stellate cells from the viewpoint of energy metabolism, and found that adenylate isozyme B (AKisoB) is closely related to hepatic stellate cell activation.
Knockdown of AKisoB by microarray analysis increased αSMA by 2.7-fold and Col1A1 by 2.1-fold. When AKisoB was purified by a column attached to protein IIA and evaluated by Western blotting, several bands were confirmed in addition to the AKiso band. The above results proved that AKisoB is involved in the activation of hepatic stellate cells. This study is expected to lead to the discovery of therapeutic agents for improving fibrosis in liver cirrhosis and the analysis of the mechanism of liver fibrosis.

Academic Significance and Societal Importance of the Research Achievements

肝硬変は肝臓の線維化により発症するが、肝線維化の改善についての詳細なメカニズムは未だ解っていない。肝線維化と関係するといわれるαSMAについて着目して研究したところ、アデニル酸アイソザイムB(AKisoB)が肝星細胞活性化と関係が深いことを見出した。本研究により肝硬変の線維化改善治療薬の創薬、および肝線維化のメカニズム解析につながってゆくことが期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (7 results)

All 2019 2018 2017

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (5 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Analysis of tolvaptan non-responders and outcomes of tolvaptan treatment of ascites.2018

    • Author(s)
      Iwamoto T, Maeda M, Saeki I, Hidaka I, Tajima K, Ishikawa T, Takami T, Sakaida I.
    • Journal Title

      J Gastroenterol Hepatol.

      Volume: - Issue: 7 Pages: 1231-1235

    • DOI

      10.1111/jgh.14524

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-Term Administration and Outcomes of Tolvaptan for Hepatic Edema2017

    • Author(s)
      Takuya Iwamoto
    • Journal Title

      Journal of Liver

      Volume: vol6, Issue4 Issue: 04 Pages: 1-4

    • DOI

      10.4172/2167-0889.1000220

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 腎機能からみたトルバプタン投与時のフロセミド増減に関する検討2019

    • Author(s)
      岩本 拓也、石川 剛、坂井田 功
    • Organizer
      第26回 日本門脈圧亢進症学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Clinical Outcomes of Balloon-Occluded Retrograde Transvenous Obliteration for the Patients with Decompensated Cirrhosis.2019

    • Author(s)
      Takuya Iwamoto, Tsuyoshi Ishikawa, Isao Sakaida
    • Organizer
      The 55th Annual Meeting of Japan Socoety of Hepatology
    • Related Report
      2019 Annual Research Report
  • [Presentation] トルバプタンが肝硬変患者の予後に与える影響の検討2018

    • Author(s)
      岩本 拓也、石川 剛、坂井田 功
    • Organizer
      門脈圧亢進症学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Recurrence prediction equation of esophageal varices2018

    • Author(s)
      Takuya Iwamoto, Tsuyoshi Ishikawa, Isao Sakaida
    • Organizer
      ISDE2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] トルバプタンの有効使用法、予後に与える影響の検討2018

    • Author(s)
      岩本 拓也、石川 剛、坂井田 功
    • Organizer
      肝臓学会総会
    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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