Elucidation of the mechanism of increased expression of RAGE in the development of NASH and development of liver fibrosis markers

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K07914
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Kochi University
• Principal Investigator: Hirose Akira 高知大学, 教育研究部医療学系臨床医学部門, 講師 (30457395)
• Co-Investigator(Kenkyū-buntansha): 越智 経浩 高知大学, 教育研究部医療学系基礎医学部門, 助教 (30617840) ; 小野 正文 香川大学, 医学部, 寄附講座教員 (70304681)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: NASH / RAGE / 肝線維化

Outline of Final Research Achievements

In RAGE KO mice fed a control diet, RAGE RNA expression levels were lower than in MT mice. In WT mice, the expression level of RAGE RNA increased upon administration of the MCD diet, whereas in RAGE KO mice, the expression level of RAGE RNA was significantly lower. In addition, the expression level of fibrosis-related markers in the liver was significantly suppressed in RAGE KO mice compared to MT mice, and the expression levels of both RNA and protein in liver tissues of mDia1, a membrane-bound protein for RAGE, were also lower. These results suggest that the RAGE-mediated mDia1-mediated signal transduction pathway is important in the progression of liver fibrosis in NASH.

Free Research Field

non-alcoholic steatohepatitis

Academic Significance and Societal Importance of the Research Achievements

これまで我々は、NASH患者および動物モデルの肝臓でRAGEの発現が亢進し、RAGE欠損マウスではNASHの肝線維化進展が抑制される事を報告し、RAGEがNASHの病態および肝線維化進展において重要な役割を果たしている事を明らかにしてきた。NASHの線維化進展のメカニズムの詳細はいまだ不明な点が多い。その解明は将来NASH患者の線維化進展抑制を目的とした治療ターゲットとなりうる可能性があり、社会的意義は大きい。