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

2020 Fiscal Year Final Research Report

• 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
• Keywords: NASH / Warburg効果 / microRNA / MIR122-5p / PKM2 / Kupffer細胞

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.

Free Research Field

一般・消化器外科学　肝臓外科学

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。