Regulation of reactive oxidative species (ROS) production in tissue-repairing process in the liver

2014 Fiscal Year Final Research Report

• Project/Area Number: 24790721
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Juntendo University
• Principal Investigator: AOYAMA Tomonori 順天堂大学, 医学部, 准教授 (10622673)
• Co-Investigator(Renkei-kenkyūsha): DAVID Brenner カリフォルニア大学サンディエゴ校, 医学部, 教授
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 肝組織修復機転 / 肝星細胞 / 酸化ストレス

Outline of Final Research Achievements

Hepatic stellate cells (HSCs) and Kupffer cells (KCs) have important roles in tissue-repairing process in the liver. Impaired this process caused by excessive reactive oxygen species (ROS) induces liver fibrosis and regeneration failure. NADPH oxidase (NOX) generates ROS. The NOX components form an active complex, including Rac1. Superoxide dismutase 1 (SOD1) interacts with the NOX-Rac1 complex. To clarify the interaction of SOD1-NOX-Rac1 in HSCs and KCs, we investigated liver fibrosis and regeneration using SOD1 mutant mice. Enhanced liver fibrosis and ROS production were found in SOD1 mutant mice treated by chronic carbon tetrachloride injections. In HSCs, SOD1 mutation induced excessive Rac1 activity, thereby causing enhanced NOX activation, ROS and collagen generation. Liver regeneration was not changed in SOD1 mutant mice. In conclusion, SOD1 regulates Rac1 and NOX activity in HSCs. SOD1-NOX-Rac1 interaction has a pivotal role in ROS generation of HSCs.

Free Research Field

消化器内科学