Elucidation of hepatocarcinogenesis mechanism in NASH and inhibition of hepatocarcinogenesis by antioxidative nanoparticles

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H03372
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: University of Tsukuba
• Principal Investigator: Suzuki Hideo 筑波大学, プレシジョン・メディスン開発研究センター, 客員教授 (00400672)
• Co-Investigator(Kenkyū-buntansha): 磯辺 智範 筑波大学, 医学医療系, 教授 (70383643) ; 岡田 浩介 筑波大学, 医学医療系, 准教授 (80757526) ; 正田 純一 筑波大学, 医学医療系, 客員教授 (90241827)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: NASH / RNP / p62 / Nrf2

Outline of Final Research Achievements

Oral administration of antioxidative nanoparticles (RNPO) inhibited liver fibrosis and prevented HCC development in p62/Sqstm1 and Nrf2 double knockout (DKO) mice through exerting potent anti-oxidative actions and suppressing inflammation by scavenging ROS. In the immunohistochemistry of Nrf2 in chronic liver diseases, hepatic inflammation and fibrosis were more severe in the low-intensity NRF2 group than in the high-intensity NRF2 group. The dense staining of NRF2 in the nuclei of non-tumor hepatocytes positively correlated with liver inflammation and fibrosis. Taken together, RNPO may be a potent biomaterial which attenuates aggravation of chronic liver diseases in the individuals associated with decreased antioxidative defense action.

Free Research Field

健康応用科学

Academic Significance and Societal Importance of the Research Achievements

抗酸化レドックス粒子(RNPO)は環境応答能を有する抗酸化剤を含むナノ粒子である．本研究では，悪玉ROSsに対して優れた選択的消去能を発揮して，NASHモデルにおいて肝炎症・線維化を抑止することが実験的に解明できた．また，RNPOには腸内細菌叢の多様性を回復させ，Gut-Liver axisを介して, 肝障害を引き起こす有害な種々の腸管由来の生物学的因子の影響を軽減するポテンシャルがあることも解明できた．今後のNASHに対する予防・治療のための新薬候補となる可能性が示唆された．