The Role of neutrophil extracellular trap(NETs) in the pathogenesis of steatosis-related diseases

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17474
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Juntendo University
• Principal Investigator: Fukada Hiroo 順天堂大学, 医学部, 准教授 (20727482)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: NETs / NETosis / 脂肪肝 / NASH / NAFLD / アルコール性肝炎

Outline of Final Research Achievements

In this study, we established a measurement system for NETs in serum by ELISA, referring to existing papers. We measured NETs in various mouse models of alcoholic liver injury (NIAAA model, mice treated with oral ethanol followed by intraperitoneal LPS, and NIAAA model with concanavalin), but the detection of NETs was poor. We need to further investigate the cause of the weak detection of NETs. As for clinical specimens, the production of NETs was observed in serum from patients with severe alcoholic hepatitis, but NETs were not detected in serum from patients with acute alcoholic hepatitis. Since stable production of NETs could not be detected in this study, it is necessary to consider the development of other measurement systems and measurement in liver tissue.

Free Research Field

消化器病学

Academic Significance and Societal Importance of the Research Achievements

肝臓の慢性的な炎症は線維化を引き起こし、肝予備能を低下させ肝不全に至る。NETosisは好中球を中心とした炎症細胞が中心静脈に炎症を起こすアルコール性肝炎や非アルコール性脂肪肝炎の病態形成に重要な役割を果たしている可能性がある。本研究ではNETosisの定量法を用い、各種アルコール性肝障害マウスや患者の血清を測定した。肝障害においてNETosisの関与を示した。本研究において得られた成果は、肝炎の病態形成にNETosisが関与している可能性を示唆しており、病態解明や創薬の開発に寄与する可能性があり、学術的、社会的意義は高いと考えられる。