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Constructing in vitro non-alcoholic steatohepatitis model using human cultured hepatocyte

Research Project

Project/Area Number 18K15814
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionHiroshima University

Principal Investigator

Murakami Eisuke  広島大学, 病院(医), 助教 (30813175)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords非アルコール性脂肪肝炎 / 肝星細胞 / TM6SF2 / 非アルコール性脂肪性肝炎
Outline of Final Research Achievements

Non-alcoholic steatohepatitis, which is characterized by fat accumulation in hepatocytes, necro-inflammatory change with monocyte infiltration, and liver fibrosis due to hepatic stellate cell activation, is an increasing chronic progressive liver disease of unknown cause. In this study, the cell-to-cell interactions were verified using in vitro co-culture experiments which conditions were similar to those in liver with non-alcoholic steatohepatitis. In the co-culture of activated monocyte, cultured hepatocyte, and hepatic stellate cell, activation of hepatic stellate cells was observed in the presence of high saturated fatty acid, palmitic acid condition. Furthermore, co-culture with TM6SF2- knocked down cell lines showed activation of hepatic stellate cells and increased fatty acid synthesis in hepatocytes at the same time. This result might be considered to be one of the suitable culture systems similar to the pathophysiology of human non-alcoholic steatohepatitis.

Academic Significance and Societal Importance of the Research Achievements

近年、脂肪肝を特徴とする非アルコール性脂肪性肝炎が増加し、健康上の問題の一つとなっている。その背景には、正確に病態を再現した実験系が確立されていない点が挙げられる。非アルコール性脂肪性肝炎の正確な機序はまだ不明であるが、肝細胞の脂肪蓄積と膨化、腸管細菌由来因子の流入と単核球の肝内浸潤、肝星細胞活性化による膠原線維増加と肝線維化が進行し、遺伝的背景も関与する事が明らかになっている。肝細胞、単核球、肝星細胞の各培養細胞を共培養し、遺伝的なリスク因子であるTM6SF2遺伝子の条件を加味し、非アルコール性脂肪性肝炎の病態をより正確に模倣したモデルを構築することは、社会的に意義があると考えられる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (10 results)

All 2021 2020 2019

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (8 results)

  • [Journal Article] In vitro analysis of hepatic stellate cell activation influenced by transmembrane 6 superfamily 2 polymorphism.2021

    • Author(s)
      Liu S, Murakami E, Nakahara T, Ohya K, Teraoka Y, Makokha GN, Uchida T, Morio K, Fujino H, Ono A, Yamauchi M, Kawaoka T, Miki D, Tsuge M, Hiramatsu A, Abe-Chayama H, Hayes NC, Imamura M, Aikata H, Chayama K.
    • Journal Title

      Mol Med Rep.

      Volume: 23(16) Issue: 1 Pages: 1-7

    • DOI

      10.3892/mmr.2020.11654

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Risk factors for histological progression of non-alcoholic steatohepatitis analyzed from repeated biopsy cases.2020

    • Author(s)
      Daijo K, Nakahara T, Inagaki Y, Nanba M, Nishida Y, Uchikawa S, Kodama K, Oya K, Morio K, Fujino H, Ono A, Murakami E, Yamauchi M, Kawaoka T, Miki D, Tsuge M, Hiramatsu A, Hayes CN, Imamura M, Aikata H, Ochi H, Chayama K.
    • Journal Title

      J Gastroenterol Hepatol.

      Volume: - Issue: 8 Pages: 1412-1419

    • DOI

      10.1111/jgh.14968

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Transmembrane 6 superfamily 2 の一塩基多型に影響される肝星細胞活性化の基礎的解析2021

    • Author(s)
      村上英介、中原隆志、茶山一彰
    • Organizer
      第107回日本消化器病学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 2型糖尿病合併非アルコール性脂肪肝炎に対する治療前後の血清中micro RNA 122の解析2020

    • Author(s)
      村上英介、中原隆志、茶山一彰
    • Organizer
      第106回日本消化器病学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 食道胃静脈瘤治療を行った 非B非C型慢性肝疾患の臨床的特徴,2020

    • Author(s)
      村上英介、中原隆志、茶山一彰
    • Organizer
      第27回日本門脈圧亢進症学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 推定内臓脂肪重量を用いた非アルコール性脂肪性肝炎の病態評価2019

    • Author(s)
      村上英介
    • Organizer
      第105回日本消化器病学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 治療介入を要する門脈圧亢進症を伴った非アルコール性脂肪性肝炎の臨床的特徴,2019

    • Author(s)
      村上英介
    • Organizer
      第55回日本肝臓学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 2型糖尿病合併NASHに対するGLP-1受容体作動薬とSGLT2阻害薬の治療効果の解析2019

    • Author(s)
      村上英介
    • Organizer
      第23回日本肝臓学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 基準未満の習慣飲酒を伴う非アルコール性脂肪肝炎の臨床的特徴2019

    • Author(s)
      村上英介
    • Organizer
      第42回日本肝臓学会西武会
    • Related Report
      2019 Research-status Report
  • [Presentation] 治療介入を要する門脈圧亢進症を伴った非アルコール性脂肪性肝炎の臨床的特徴2019

    • Author(s)
      村上英介
    • Organizer
      第55回日本門脈圧亢進症学会総会
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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