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

2015 Fiscal Year Final Research Report

• Project/Area Number: 26861081
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kyushu 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
• Keywords: 肝再生 / apelin / APJ / クッパー細胞

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.

Free Research Field

肝再生