Discovery of new insulin-resistance marker which determines the effect of IFN for chronic hepatitis C

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461012
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The Nippon Dental University (2014-2015); Showa University (2013)
• Principal Investigator: Ohkoshi Shogo 日本歯科大学, 新潟生命歯学部, 教授 (70231199)
• Co-Investigator(Kenkyū-buntansha): MATSUDA Yasunobu 新潟大学, 医歯学系, 准教授 (40334669) ; YAMAGIWA Satoshi 新潟大学, 医歯学系, 准教授 (10419327)
• Co-Investigator(Renkei-kenkyūsha): YANO Masahiko 昭和大学, 歯学部, 助教 (70529693)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: HCV / RBP-4 / Peg-IFN / インスリン抵抗性

Outline of Final Research Achievements

We examined whether RBP4(Retinol binding protein 4) was a significant factor which determined the outcome of the CH C patients with genotype 1b who were treated with PEG-IFN plus ribavirin.
Because RBP4 was a marker of insulin resistance, we speculated that this might be the key molecule which determined the association between IFN therapy and insulin resistance. We performed in vitro experiments to examine whether RBP4 suppressed IFN signalling, resulting in the resistance of HCV replication against IFN. As a result, in RBP4-knockdown hepatoma cell, ISG genes were activatied and HCV replication was enhanced when compared to RBP4 (+) cells. Thus we found that RBP4 interfered the action of IFN against HCV and result in IFN resistance.
However, RBP4 was not proved to be a significant factor for the prediction of clinical data from more number of patients. In conclusion, we could not verify the significance of RBP4 levels for the prediction of IFN therapy.

Free Research Field

消化器病学