Development of novel treatment for non-alcoholic steatohepatitis targeting microRNA

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15609
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Chiba University
• Principal Investigator: Nakamura Masato 千葉大学, 医学部附属病院, 特任助教 (10756703)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 非アルコール性脂肪肝炎 / 肝硬変 / microRNA

Outline of Final Research Achievements

Non-alcoholic steatohepatitis (NASH) has becoming a leading cause of liver cirrhosis and hepatocellular carcinoma worldwide. In this study, we aimed to clarify the involvement of microRNAs (miRs) in NASH and to find out their potentials as therapeutic targets.
We revealed that expression of miR-200 family is significantly enhanced in liver tissues of mice fed with methionine-choline deficient diet. Upregulation of miR-200b expression also was observed in NASH patients, especially those with advanced liver fibrosis. Furthermore, it was found that miR-200b inhibitor administration to NASH model mice reduced liver damage and suppressed liver inflammation and fibrosis.
These data indicate that miR-200b is involved in the progression of NASH by affecting liver damage, inflammation and fibrosis, and that inhibition of miR-200b could be a novel treatment for NASH patients.

Free Research Field

肝臓病学

Academic Significance and Societal Importance of the Research Achievements

本研究は、肝硬変や肝癌の主要な原因となりつつある非アルコール性脂肪肝炎（NASH）において、細胞間情報伝達因子として注目されているmicroRNAの異常が関与していることを明らかにした。また、マウスモデルを用いて、microRNA制御がNASHの病態改善に有効であることを実証し、治療法が確立していないNASHの克服に新たな可能性を示した。本研究成果により、NASHに対する治療選択肢が増えることが期待される。