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Relationship between sudden death syndrome of alcohol drinker and the role of bone marrow-derived stellate cells in alcohol-induced fatty liver

Research Project

Project/Area Number 20590680
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Legal medicine
Research InstitutionYamaguchi University

Principal Investigator

FUJIMIYA Tatsuya  Yamaguchi University, 大学院・医学系研究科, 教授 (50219044)

Co-Investigator(Kenkyū-buntansha) LIU Jinyao  山口大学, 大学院・医学系研究科, 講師 (60379956)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2008: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Keywordsアルコール / 大酒家 / 突然死 / 脂肪肝 / アルコール性臓器障害 / 骨髄幹細胞 / 法医学 / 伊東細胞 / 細胞融合
Research Abstract

Chronic alcohol consumption activates hepatic stellate cells (HSCs) and cause fatty degeneration in the liver. However, the origin of HSCs and the mechanism of fatty changes of the liver have not been fully elucidated. Here, we examined the roles of bone marrow-derived cells (BMDCs) in a mouse model with chronic alcohol consumption. We performed bone marrow transplantation from transgenic mice expressing green fluorescence protein (GFP) to female wild-type and ROSA mice and treated them with ethanol (EtOH) for 8 or 16 wk. GFP-expressing BMDCs increased in the liver with EtOH treatment in a time-dependent manner. In response to excess alcohol consumption, ~68% of the BMDCs became activated HSCs in that they expressed α-smooth muscle actin. Meanwhile, ~67% and ~66% of these BMDCs expressed Tnf-α and transforming growth factor (Tgf)-β1, respectively, and the activities were further supported by the excessive mRNA expression of Tnf-α and Tgf-β1 in RT-PCR, respectively. Cell fusion occurs between BMDCs and nonparenchymal cells but scarcely occurs between BMDCs and hepatocytes, demonstrated by double staining of β-gal/GFP and further supported by the Y-chromosome staining. The EtOH withdrawal normalized most of the abnormalities produced by chronic alcohol consumption. These results indicate that excess alcohol consumption stimulates both the homing of HSCs from the bone marrow and their profibrogenic cytokine production in a mouse model of alcohol-induced fatty liver disease.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (11 results)

All 2010 2009 2008 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (4 results) Remarks (2 results)

  • [Journal Article] アルコール性脂肪肝における骨髄細胞の動員および分化・増殖2010

    • Author(s)
      劉金耀、藤宮龍也, 他
    • Journal Title

      アルコールと医学生物学 29巻

      Pages: 27-32

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] QT Interval Dispersion and Cardiac Sympathovagal Balance Shift in Rats with Acute Ethanol Withdrawal.2010

    • Author(s)
      Shirafuji S, Liu J, Fujimiya T.
    • Journal Title

      Alcohol Clin Exp Res 34(2)

      Pages: 223-230

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] QT Interval Dispersion and Cardiac Sympathovagal Balance Shift in Rats with Acute Ethanol Withdrawal.2010

    • Author(s)
      Shirafuji S, Fujimiya T.
    • Journal Title

      Alcohol Clin Exp Res.

      Volume: 34(2) Pages: 223-230

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] アルコール性脂肪肝における骨髄細胞の動員および分化・増殖2010

    • Author(s)
      劉金耀
    • Journal Title

      アルコールと医学生物学 29

      Pages: 27-32

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathological roles of bone marrow-derived stellate cells in a mouse model of alcohol-induced fatty liver.2009

    • Author(s)
      Fujimiya T, Liu J, et al.
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol. 297

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Presentation] Rats in Acute Withdrawal from Ethanol Exhibit the High Risk of Myocardial Fibrosis Formation and the Cardiac Sympathetic Predominance2010

    • Author(s)
      Liu J, Fujimiya T.
    • Organizer
      2010 world congress of International Society for Biomedical Research on Alcoholism
    • Place of Presentation
      Paris, France
    • Year and Date
      2010-09-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] アルコール性脂肪肝における骨髄細胞の動員および分化・増殖2009

    • Author(s)
      劉金耀、藤宮龍也, 他
    • Organizer
      アルコール医学生物学研究会
    • Place of Presentation
      千葉、千葉大学
    • Year and Date
      2009-11-13
    • Related Report
      2010 Final Research Report
  • [Presentation] アルコール性脂肪肝における骨髄細胞の動員および分化・増殖2009

    • Author(s)
      劉金耀
    • Organizer
      アルコール医学生物学研究会
    • Place of Presentation
      千葉大
    • Year and Date
      2009-11-13
    • Related Report
      2009 Annual Research Report
  • [Presentation] アルコール性脂肪肝における肝臓星細胞の活性化2008

    • Author(s)
      劉 金耀
    • Organizer
      第43回日本アルコール・薬物医学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2008-09-19
    • Related Report
      2008 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      http://ds.cc.yamaguchi-u.ac.jp/~legal/

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://ds.cc.yamaguchi-u.ac.jp/~legal/

    • Related Report
      2010 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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