Study of the role of the vagal liver branch in the onset and progression mechanism of nonalcoholic steatohepatitis.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08014
• 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: Keio University
• Principal Investigator: TERATANI Toshiaki 慶應義塾大学, 医学部(信濃町), 講師 (40624408)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 非アルコール性脂肪肝炎 / 脳肝相関 / 肝星細胞

Outline of Final Research Achievements

Non-alcoholic steatohepatitis (NASH) is a phenotype of lifestyle-related disease in the liver. NASH is a disease that progresses to cirrhosis and eventually hepatocellular carcinoma. In Japan, where the number of NASH patients is increasing rapidly, it is necessary to elucidate the pathogenesis and progression mechanism of NASH. Therefore, in this study, we aimed to elucidate the role of the hepatic vagal branch in NASH pathology.
Resection of the hepatic vagal branch exacerbated the liver fibrotic pathology of MCD-NASH. Analysis of neurotransmitter receptor gene expression in hepatic stellate cells revealed high expression of muscarinic acetylcholine receptor subtype 2 (mAchR2). In mAchR2-deficient mice, CCl4 or MCD-induced liver fibrosis was even exacerbated compared to wild-type mice. It was suggested that the muscarinic signal in hepatic stellate cell has an inhibitory effect on liver fibrosis.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

本研究では、近年注目される脳肝相関に着目した。肝臓内の神経線維維持において、肝星細胞が分泌されるグリア細胞株由来神経栄養因子が重要な役割を果たすことが本研究により明らかとされた。さらに、肝星細胞内のムスカリンシグナルが活性化および細胞増殖を抑制していることが明らかとなった。これまで、脳からの指令は、肝細胞や免疫細胞に作用することが示されてきたが、本研究により脳から伝播されるシグナルは肝星細胞のような線維芽細胞にも作用することが示された。