Elucidation of the mechanism of hepatocarcinogenesis suppression by mitochondrial ferritin

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07995
• 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: Kawasaki Medical School
• Principal Investigator: HARA YUICHI 川崎医科大学, 医学部, 特任研究員 (60550952)
• Co-Investigator(Kenkyū-buntansha): 日野 啓輔 川崎医科大学, 医学部, 特任研究員 (80228741)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: mitochondria / mitophagy / HCC

Outline of Final Research Achievements

When the muscle mass of mice with hepatocarcinoma was evaluated based on muscle weight relative to body weight (muscle weight (mg)/body weight (g)), the average muscle weight (mg)/body weight (g) of this mouse model was 2.12, but when DFP was added to this mouse model, it significantly increased to 2.91 (p<0.05). Furthermore, when DFP was added to this mouse model in which mitophagy was specifically inhibited in the liver, muscle weight (mg)/body weight (g) decreased to 2.01, with no significant difference from control mice. Furthermore, compared with mice with hepatocarcinoma that were applied with (DMBA) and fed a high-fat diet, serum selenoprotein P in a model in which DFP was added was significantly reduced to 0.62-fold (<0.05). Furthermore, in a model in which mitophagy was specifically suppressed in the liver, serum selenoprotein P was 1.12-fold, not significantly different from untreated mice.

Free Research Field

hepatology

Academic Significance and Societal Importance of the Research Achievements

FTMTは以前からその存在は知られていたが、その発現機構及び機能についてはほとんど知られていない。肝発癌過程でのFTMTの発現の意義については未だ不明である。本研究でその機構が明らかになれば世界で初めての知見となる。 またFTMTの発現を促す薬剤は鉄キレート剤のみしか明らかになっていないが、鉄キレート剤はその副作用として、貧血を引き起こすことが予想される。この研究により、FTMT の発現を促す薬剤が明らかとなれば、安全で発癌抑制を期待できる薬剤が開発できることになる。FTMT発現誘導による肝発がん抑制はこれまで行われておらず、これもまた世界で初めての試みである。