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Explication of a new molecule mechanism of liver regeneration and usability of therapeutic option to facilitate efficient liver regeneration after liver surgery

Research Project

Project/Area Number 26861081
Research Category

Grant-in-Aid for Young Scientists (B)

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

Principal Investigator

Yoshiya Shohei  九州大学, 医学(系)研究科(研究院), 共同研究員 (20717079)

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肝再生 / apelin / APJ / クッパー細胞 / クッパ-細胞
Outline of Final Research Achievements

We used the specific APJ antagonist F13A on liver regeneration after hepatectomy in mice. Results: F13A-treated mice had significantly higher serum concentrations of TNF-α and IL-6 than control mice, resulting from activation of Kupffer cells. Compared with untreated mice, F13A enhanced the STAT3 and MAP kinase pathways, stimulated cell-cycle progression, and promoted hepatocyte proliferation and liver regeneration without inducing apoptosis or inflammation in regenerating livers. In vitro, Kupffer cells expressed APJ and were activated directly by F13A treatment, releasing TNF-α and IL-6. Moreover, F13A-treated mice had a higher survival rate than untreated mice in the extended hepatectomy model.
Conclusion: F13A treatment promotes early phase liver regeneration after hepatectomy, increasing levels of TNF-α and IL-6 by activating Kupffer cells. F13A treatment may become a therapeutic option to facilitate efficient liver regeneration after liver surgery.

Report

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

    (1 results)

All 2015

All Journal Article (1 results) (of which Peer Reviewed: 1 results)

  • [Journal Article] Blockade of the apelin-APJ system promotes mouse liver regeneration by activating Kupffer cells after partial hepatectomy.2015

    • Author(s)
      Yoshiya S, Shirabe K, Imai D, Toshima T, Yamashita Y, Ikegami T, Okano S, Yoshizumi T, Kawanaka H, Maehara Y.
    • Journal Title

      J Gastroenterol.

      Volume: 50 Issue: 5 Pages: 573-82

    • DOI

      10.1007/s00535-014-0992-5

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed

URL: 

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

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