Functional analysis of transcription factor Nrf2 and production of new therapy in primary biliary cirrhosis

• Project/Area Number: 26860499
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Kawata Kazuhiot 浜松医科大学, 医学部附属病院, 助教 (90722968)
• Research Collaborator: SHIMOYAMA shin
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 原発性胆汁性肝硬変 / Nrf2 / 原発性胆汁性肝硬変症

Outline of Final Research Achievements

We have constructed xenobiotic-induced murine model of primary biliary cholangitis (PBC) in Nrf2 knock out (Nrf2 -/-) mouse, Nrf2 increase mouse used with sulforaphane and C57BL/6 mouse immunized with 2OA. Nrf2 -/- mouse with 2OA immunization developed cholangitis, in contrast, Nrf2 increase mouse with 2OA immunization demonstrated less cholangitis compared with C57BL/6 mouse with 2OA immunization. Production of IFNγ in hepatic T cell from Nrf2 -/- mouse with 2OA immunization was significantly higher than C57BL/6 mouse with 2OA immunization. In contrast, hepatic T cell from Nrf2 increase mouse with 2OA immunization demonstrated less IFNγ production compared with C57BL/6 mouse with 2OA immunization. It is known that UDCA treatment can enhance hepatic Nrf2 activation in PBC. According to these result, UDCA treatment reduces IFNγ production by enhanced Nrf2 activation in hepatic T cells and ameliorates cholangitis in PBC. Nrf2 activation in hepatic T cell may be a new therapy in PBC.