Elucidation of NASH pathogenesis by the cancer specific energy metabolic machinery regulatory gene

Research Project

Project/Area Number	17K10679
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Digestive surgery
Research Institution	Osaka Medical College
Principal Investigator	Hirokawa Fumitoshi 大阪医科大学, 医学部, 准教授 (20322373)
Co-Investigator(Kenkyū-buntansha)	高井真司大阪医科大学, 医学研究科, 教授 (80288703)
Project Period (FY)	2017-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000) Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	NASH / Warburg効果 / microRNA / MIR122-5p / PKM2 / Kupffer細胞 / 非アルコール性脂肪性肝炎 / ワーバーグ効果
Outline of Final Research Achievements	The purpose of this study is to examine the association with the pathophysiology of NASH and the cancer-specific energy metabolism (Warburg effect)-affiliated genes using NASH models (rats and mice). The glycolytic pathway, the main constituent of the Warburg effect, was activated in the NASH group. PKM2 and phosphorylation-PKM2, which were limited-enzyme of the Warburg effect, were significantly up-regulated in the NASH group. Furthermore, MIR122-5p, which was one of the microRNAs, coordinated the expression of PKM2. In addition, the main constituent of this change was Kupffer cells. It was suggested that the Warburg effect was activated in Kupffer cells of NASH.
Academic Significance and Societal Importance of the Research Achievements	非アルコール性脂肪性肝炎（NASH）は進行性の慢性肝炎であり、肝硬変から肝細胞癌を発症するにもかかわらずいまだ明確な治療法は確立されていない。本研究ではNASH発症とKupffer細胞の代謝変化をmicroRNAの観点から解明した。この研究結果はKupffer細胞の代謝機構を標的とするNASH治療法への一助となり社会的意義の期待される成果である。