Study of epigenetic regulation in nonalcoholic steatohepatitis

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15762
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Tokai University
• Principal Investigator: CHIKADA Hiromi 東海大学, 医学部, 特別研究員 (60712776)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 非アルコール性脂肪性肝炎NASH / エピジェネティック制御 / Bcl6

Outline of Final Research Achievements

We previously found that B cell lymphoma 6 (Bcl6) was involved in Nonalcoholic steatohepatitis (NASH) progression by the analysis of liver specific Bcl6 knockout mice. In this study, we tried to analyze the Bcl6 function through the epigenetic regulation to elucidate the NASH progression mechanism. We performed the biochemical purification to identify Bcl6 interactants using Bcl6-overexpressed 293T cells. BCoR and p53, which were already known to interact with Bcl6 and the new factors including zinc finger transcription factors were identified as Bcl6 interactants. We began to identify the hepatic Bcl6 interactants and confirm the relation between the epigenetic activity and NASH progression.

Free Research Field

肝臓生物学

Academic Significance and Societal Importance of the Research Achievements

NASHは、脂質代謝の破綻に起因するメタボシックシンドロームの肝臓での表現型と考えられる。NASH患者の増加が予想される一方で、未だ根本的な治療法はない。本研究ではBcl6の分子機能としてエピジェネティックな活性に注目して、NASH発症との関連性を検証することにより、NASHの適切な治療標的を見出すことができると考えた。また、学術的にも肝臓のBcl6の分子機能については不明な点が多く、新規の知見を得ることができると期待した。