Establishment of new treatment targeting lifestyle diseases and coagulation fibrinolytic system related to the development of NASH

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461018
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Nara Medical University
• Principal Investigator: Noguchi Ryuichi 奈良県立医科大学, 医学部附属病院, 研究員 (30423908)
• Co-Investigator(Renkei-kenkyūsha): MATSUMOTO MASANORI 奈良県立医科大学, 医学部, 教授 (60316081) ; NAMISAKI TADASHI 奈良県立医科大学, 医学部, 講師 (20526850) ; MORIYA KEI 奈良県立医科大学, 医学部, 講師 (40526852) ; KITADE MITSUTERU 奈良県立医科大学, 医学部, 助教 (40526795) ; MASHITANI TSUYOSHI 奈良県立医科大学, 医学部, 助教 (20401929)
• Research Collaborator: NISHIMURA NORIHISA
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: NASH / 生活習慣病 / ARB / DPP-Ⅳ阻害剤 / SGLT-2阻害剤 / PAI-1阻害剤

Outline of Final Research Achievements

In the rat NASH model, ARB and DPP-IV inhibitor innhibited liver fibrosis along with suppression of activated hepatic stellate cells (Ac-HSCs) and TGF-β expression, and treatment with both drugs further suppressed significantly as compared with either single agent. SGLT-2 inhibitor, which is a drug for treating diabetes mellitus, indirectly suppressed liver fibrosis through the insulin resistance-improving effect. PAI-1 inhibitor markedly inhibited the development of liver fibrosis along with suppression of Ac-HSC. Our in vitro data showed that PAI-I inhibitor directly suppressed proliferation of Ac-HSCs, expression of TGF-β mRNA and α1 collagen mRNA. Furthermore, clinical studies suggested the possibility of DPP-IV inhibitor for treating fatty liver disease with type 2 diabetes.

Free Research Field

肝臓病学