Viral impact of hepatic non-parenchymal cells on Hepatitis B virus infected hepatocytes

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07940
• 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: Kanazawa University
• Principal Investigator: KAWAGUCHI Kazunori 金沢大学, 医学系, 協力研究員 (90579632)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: B型肝炎ウイルス / 血管内皮細胞 / 類洞内皮細胞 / 肝細胞増殖因子

Outline of Final Research Achievements

Nonparenchymal cells such as endothelial cells, bile duct cells, and immune cells exist in liver tissue in addition to hepatocyte, however the interactions among these cells by hepatitis B virus infection have not been fully investigated. Previous studies we examined changes in gene expression by single cell analysis among liver component cells and found that intercellular signaling are closely related to the pathogenesis between these cells. In this study, we evaluated how vascular endothelial cells and sinusoidal endothelial cells could affect hepatitis B virus infected hepatocytes. Co-culture of endothelial cells with infected hepatocytes showed a significant increase in viral replication, suggesting the involvement of hepatocyte growth factor, and the PI3K/Akt/mTOR pathway was also found to be mediated as important signaling in hepatitis B virus infected hepatocytes.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

核酸アナログ製剤によりB型肝炎の鎮静化がなされるが、治療後も肝細胞核内に完全二本鎖の形でウイルスが残存しており、発癌や再活性化を引き起こす。この問題を解決するために、肝組織内の構成細胞における感染による変化、細胞間の相互作用やシグナル伝達系を明確にすべきと考えた。本研究では特に、肝組織を構成する各種細胞間の作用に関わる実験的検討を行い、詳細に条件設定しながら実行し、どのような相互作用が存在するかが明らかとなった。本研究はこのウイルス残存の問題を解決し、従来の薬剤では解決できない新たな創薬にも関連するので、社会的意義のある研究とされた。