A new liver regeneration molecular mechanism involving hepatic stellate cells, Kupffer cells, and glucose-regulated protein 78 as a new hepatotrophic factor

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09189
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Gunma University
• Principal Investigator: Harimoto Norifumi 群馬大学, 医学部附属病院, 准教授 (00419582)
• Co-Investigator(Kenkyū-buntansha): 五十嵐 隆通 群馬大学, 医学部附属病院, 助教 (20648472) ; 新木 健一郎 群馬大学, 大学院医学系研究科, 助教 (60431706) ; 渡辺 亮 群馬大学, 医学部附属病院, 助教 (60738847) ; 調 憲 群馬大学, 大学院医学系研究科, 教授 (70264025)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 肝細胞 / 肝再生

Outline of Final Research Achievements

We examined the effect of M2BPGi on human hepatocytes and KCs, and explored secretory factors from M2BPGi-activated KCs using proteomics. Furthermore, the effect on liver regeneration of glucose-regulated protein 78 (GRP78) as one of the M2BPGi-related secreted proteins was examined in vitro and in murine hepatectomy models.
Results: Although M2BPGi had no hepatocyte-promoting effect, M2BPGi promoted the production of GRP78 in KCs. The KC-driven GRP78 promoted hepatocyte proliferation. GRP78 administration facilitated liver regeneration after 70% hepatectomy and increased the survival rate after 90% hepatectomy in mice.
Conclusions: The M2BPGi-activated KCs secrete GRP78, which facilitates liver regeneration and improves the survival in a lethal mice model. Our data suggest that the new hepatotrophic factor GRP78 may be a promising therapeutic tool for lethal liver failure.

Free Research Field

肝臓外科

Academic Significance and Societal Importance of the Research Achievements

今回の検討にて新たな肝再生因子GRP78を同定し、その肝再生におけるメカニズムを解明した。この肝再生の芽蟹図はこれまで報告されたことがなく、新しい肝栄養因子GRP78が致命的な肝不全の有望な治療ツールである可能性があることを示唆した。