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Role of autophagy and Sirt-1 signal in liver regeneration

Research Project

Project/Area Number 26861083
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Digestive surgery
Research InstitutionKyushu University

Principal Investigator

Toshima Takeo  九州大学, 医学(系)研究科(研究院), 研究員 (40608965)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsオートファジー / 肝再生 / 肝障害 / 脂肪肝 / 肝切除 / 肝臓 / 肝移植
Outline of Final Research Achievements

Our findings indicate that lipid droplet suppress autophagic proteolysis in fatty liver regeneration. The survival rate after partial hepatectomy (PH) in db/db mice was 20%, which was significantly lower than in control mice. The liver regeneration within 48h after PH was significantly inhibited in db/db mice. The number of PCNA positive cells and the expression levels of cell cycle marker, cyclin D,E,A were lower in db/db mice. In regenerating liver, the protein level of LC3-II expression was higher in db/db mice, nevertheless, the expression of p62 was increased and the expression of cathepsin D, marker of proteolysis of autophagolysosome was decreased. Furthermore, electron microscopy revealed the localization of autophagosomes during liver regeneration was different. Autophagosomes mainly existed in cytoplasm in control mice, while in lipid drop in db/db mice. Autophagy therefore has the potential to serve as an important therapeutic target for the treatment of these disorders.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (5 results)

All 2015 2014

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (1 results)

  • [Journal Article] A novel serum marker, glycosylated Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP), for assessing liver fibrosis.2015

    • Author(s)
      Toshima T, Shirabe K, Ikegami T, et al.
    • Journal Title

      Journal of Gastroenterology

      Volume: 50 Issue: 1 Pages: 76-84

    • DOI

      10.1007/s00535-014-0946-y

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suppression of autophagy during liver regeneration impairs energy charge and hepatocyte senescence in mice.2014

    • Author(s)
      Toshima T1, Shirabe K, Fukuhara T, Ikegami T, Yoshizumi T, Soejima Y, Ikeda T, Okano S, Maehara Y.
    • Journal Title

      Hepatology.

      Volume: 印刷中 Issue: 1 Pages: 25-25

    • DOI

      10.1002/hep.27140

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Autophagy enhances hepatocellular carcinoma progression by activation of mitochondrialβ-oxidation2014

    • Author(s)
      Toshima T, Shirabe K, Matsumoto Y, Yoshiya S, Ikegami T, Yoshizumi T, Soejima Y, Ikeda T, Maehara Y.
    • Journal Title

      J Gastroenterol

      Volume: 49(5) Issue: 5 Pages: 907-16

    • DOI

      10.1007/s00535-013-0835-9

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Application of Postoperative MELD Scoring System for Evaluating Liver Graft Function After Living Donor Liver Transplantation.2014

    • Author(s)
      Toshima T, Ikegami T, Kimura K, et al.
    • Journal Title

      Transplant Proceedings

      Volume: 46 Issue: 1 Pages: 81-86

    • DOI

      10.1016/j.transproceed.2013.09.034

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 脂肪肝マウスの肝切除後肝再生遅延におけるオートファジーの役割2015

    • Author(s)
      松本佳大
    • Organizer
      第115回日本外科学会定期学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-04-16
    • Related Report
      2015 Annual Research Report

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Published: 2014-04-04   Modified: 2017-05-10  

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