Cell death-induced inflammation and the development of NASH and hepatocellular carcinoma

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07475
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Nagoya University
• Principal Investigator: ITOH Michiko 名古屋大学, 環境医学研究所, 特任准教授 (00581860)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 慢性炎症 / マクロファージ / 線維芽細胞

Outline of Final Research Achievements

Chronic inflammation is a common molecular basis of a variety of chronic diseases, including NASH. During the course of tissue remodeling caused by chronic inflammation, sustained interaction between parenchymal cells and stromal cells leads to tissue fibrosis. It is important to understand the heterogeneity and phenotypic changes of interstitial cells on each organ and pathogenic etiology. We have reported a histological structure termed crown-like structure (CLS), in which macrophages and fibroblasts surround dead hepatocytes with large lipid droplets, using our unique mouse model of NASH. In this study, we investigated the disease-specific activation mechanisms of CLS-forming macrophages and fibroblast, driving the progression from simple steatosis to NASH and hepatocellular carcinoma.

Free Research Field

代謝学

Academic Significance and Societal Importance of the Research Achievements

NASHは肝硬変・肝細胞癌に進展する重症型であるが、その発症機構には不明な点が多く、確立した治療法も存在しない。NASHの予後の悪さと罹患率の高さを考慮すると、患者のQOL改善および医療経済の観点から病態早期の診断・介入が必要である。本研究では病態形成早期に認められる病理学的構造に焦点を当て、NASH・肝細胞癌への発症進展につながる間質細胞の機能変化を明らかにしており、早期診断法の確立や治療法の開発に繋がることが期待される。