Elucidation of the mechanisms by which novel vascular endothelial cell markers are involved in liver fibrosis and hepatocarcinogenesis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07905
• 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: Department of Clinical Research, National Hospital Organization Kanazawa Medical Center
• Principal Investigator: Nishikawa Masashi 独立行政法人国立病院機構(金沢医療センター臨床研究部), その他部局等, 研究員 (90794511)
• Co-Investigator(Kenkyū-buntansha): 岡田 光 金沢大学, 医薬保健学総合研究科, 特任准教授 (50788916)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 新規血管内皮細胞マーカー

Outline of Final Research Achievements

This study demonstrated that TMEM164 has an inhibitory effect on NASH-induced liver carcinogenesis.
Expression analysis and immunohistochemistry using liver tissue samples from NAFLD/NASH model mice revealed that the cells in which TMEM164 functions to suppress the progression of NASH pathology are liver endothelial cells, specifically liver infiltrating vascular endothelial cells derived from bone marrow cells in the context of liver fibrosis. The endothelial cells may attract inflammatory cells such as macrophages and CD8 T cells that cause hepatocarcinogenesis, and TMEM164 may suppress these cells.

Free Research Field

肝発がん

Academic Significance and Societal Importance of the Research Achievements

これらの結果から、TMEM164は、世界で未だ報告がなく、申請者だけが初めて報告した独自のNASH-HCC病態における標的遺伝子になり得ることが明らかになった。TMEM164のあらたな生理機能の発見は、未だ治療薬がない肝線維化に対する薬剤の開発に貢献できる。