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Elucidation of activation mechanism of hepatic stellate cells through mechano-transduction

Research Project

Project/Area Number 17K15561
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General physiology
Research InstitutionOsaka City University

Principal Investigator

Urushima Hayato  大阪市立大学, 大学院医学研究科, 助教 (90755745)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsメカノトランスダクション / 肝星細胞 / 接着結合 / 肝がん細胞 / 浸透圧 / Eカドヘリン / 低浸透圧 / アポトーシス耐性 / 病態生理
Outline of Final Research Achievements

In normal liver, hepatic stellate cells, one of the mesenchymal cells, express E-cadherin, which is mainly expressed in epithelial cells, and mechanotransduction occurs by adherens to hepatocytes via this E-cadherin, leadig to the suppression of hepatic stellate cells activation. In liver injury, the loss of this adherens junction increases the sensitivity to TGF-β produced in the surroundings, which play a role of hepatic stellate cells activation.
In cirrhotic stage, hyponatremia-induced hypo-osmotic condition induce apoptosis resisatance of hepatic stellate cells and hepatocellular carcinoma cells through mechano-receptor.
Therefore, our study revealed that mechanotransuduction regulate both the pysiology and pathology of hepatic stellate cells and hepatocellular carcinoma cells.

Academic Significance and Societal Importance of the Research Achievements

肝星細胞は肝障害時に産生されたTGF-βなどの刺激因子によって活性化しコラーゲンを産生し創傷治癒に働くが、慢性肝疾患時の持続的活性化は肝線維化、さらには肝硬変を引き起こす。そのため肝星細胞の活性抑制を目的とした研究が数多く行われてきたが未だ有効な薬剤は開発されていない。今回の我々の研究は刺激因子に依らない新規の肝星細胞メカニズムを明らかにした。今回の発見は有効な肝星細胞活性化抑制剤研究の礎となる可能性がある。
また肝硬変時の低ナトリウム血症を積極的に改善することで肝発がんの重要なリスクファクターである肝硬変患者の肝がん発生リスクを減少させる可能性があると考えられる

Report

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

Research Products

(9 results)

All 2019 2018 2017

All Journal Article (1 results) Presentation (8 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] 【肝星細胞活性化と肝硬変・肝がん】肝星細胞活性化の新規initiation factor2019

    • Author(s)
      宇留島隼人・池田一雄
    • Journal Title

      細胞

      Volume: 51 Pages: 526-529

    • Related Report
      2019 Annual Research Report
  • [Presentation] 肝細胞-肝星細胞間の接着結合喪失は肝星細胞活性化に寄与する2019

    • Author(s)
      宇留島隼人, 湯浅秀人, 松原勤, 井上孝二, 和氣健二郎, 佐藤哲二, 池田一雄
    • Organizer
      第124回日本解剖学会全国学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Oligonol ameliorates hepatic fibrosis through the inhibition of FAK-YAP pathway in hepatic stellate cells2019

    • Author(s)
      Hayato Urushima, Hideto Yuasa, Misako Takayama, Tsutomu Matsubara, Kazuo Ikeda
    • Organizer
      27 th International Congress on Nutrition and Integrative Medicine
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Stellate cells initiate the activation by the loss of adherens junction with hepatocytes2019

    • Author(s)
      Hayato Urushima, Hideto Yuasa, Tsutomu Matsubara, Yaiko Hara, Koji Inoue, Kenjiro Wake, Tetsuji Sato, Kazuo Ikeda
    • Organizer
      20th International Symposium on Cells of Hepatic Sinusoid
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 肝硬変時の低ナトリウム血症による低浸透圧環境が門脈圧亢進に及ぼす影響2019

    • Author(s)
      宇留島隼人, 松原勤, 湯浅秀人、河田則文, 池田一雄
    • Organizer
      第26回日本門脈圧亢進症学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 正常肝ないし障害肝の肝星細胞におけるfilopodia関連タンパク質の発現解析2019

    • Author(s)
      湯浅秀人、宇留島隼人、松原勤、池田一雄
    • Organizer
      第33回肝類洞壁細胞研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 肝星細胞-肝細胞間の接着と肝星細胞活性化との関係について2019

    • Author(s)
      湯浅秀人、宇留島隼人、松原勤、池田一雄
    • Organizer
      第14回中四国電子顕微鏡研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 低浸透圧環境下における肝がん細胞アポトーシス抑制のメカニズム解析2018

    • Author(s)
      宇留島隼人、松原勤、河田則文、池田一雄
    • Organizer
      第7回 Kansai Liver Club
    • Related Report
      2017 Research-status Report
  • [Presentation] 低浸透圧環境は活性化肝星細胞や肝がん細胞のアポトーシスを抑制する2017

    • Author(s)
      宇留島隼人、松原勤、小田桐直志、池田一雄
    • Organizer
      第31回肝類洞壁細胞研究会
    • Related Report
      2017 Research-status Report

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

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