Effect of MCP-1 and sSiglec9 in the animal models of acute liver failure

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K07936
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Nagoya University
• Principal Investigator: Ishigami Masatoshi 名古屋大学, 医学系研究科, 准教授 (90378042)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 肝再生 / マクロファージ / 炎症-再生相関

Outline of Final Research Achievements

In this study, we investigated the effect of combination of 2 humoral factors; MCP-1, which is the well-known factors for the migration of macrophage into inflamed site, and sSiglec-9, which is the key factor of transition of macrophage from inflammatory to anti-inflammatory subset in several animal models of acute liver injury as the candidate for promoting liver regeneration directly, which does not exist in clinical practice.
Combination of these 2 factors improved the survival of mice in Concanavalin A or CCl4 induced acute liver injury models. Expression of CD206 and Arginase-1, which are the surface markers of anti-inflammatory subsets of macrophage and HGF, β-catenin, or EpCAM, which are the markers of liver regeneration, increased in the group of inoculation of these 2 factors compared with controls. In cultured hepatic stellate cells, these 2 factors inhibit the activation, and keep the quiescent state, resulting the increased expression of HGF.

Free Research Field

肝臓病学

Academic Significance and Societal Importance of the Research Achievements

現在、急性肝不全においてその治癒の鍵となる肝再生促進を直接促進させる薬剤は存在せず、そのために未だに多くの患者を失っているのが現状である。その一つの有力な候補としてMCP-1+sSiglec9の2因子併用が、多くの肝不全動物モデルにおいて有用であること、またその炎症抑制、肝再生促進のメカニズムを明らかにすることで、現在実臨床で存在しない新たな治療法、および現在でも死亡率の高い本疾患における生存率の向上に寄与することが可能となってくるであろう。