Gene regulation in the liver of human non-alcoholic steatohepatitis (NASH)

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K11758
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Kyorin University
• Principal Investigator: Yasuda Kazuki 杏林大学, 医学部, 教授 (80311611)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: NASH / 生活習慣病 / 遺伝子発現調節

Outline of Final Research Achievements

Based on our previous transcriptome study of the liver obtained from Japanese NASH (non-alcoholic steatohepatitis) subjects, we selected AKR1B15, a novel member belonging to the same family as AKR1B10. Using human hepatocyte cell line HuH7, we found the Nrf2 activation significantly increased AKR1B15 expression, and this was mediated by direct binding of Nrf2 to one ARE (Antioxidant Response Element) in the promotor region of this gene. This pathway is distinct from AKR1B10 induction, suggesting complex pathophysiology of NASH.

Free Research Field

生活習慣病、内分泌・代謝学

Academic Significance and Societal Importance of the Research Achievements

NASHは極めて頻度の高い疾患であるだけでなく、肝がんの発生母地として、また心血管病変のハイリスクとして重要であるが、病態の多くが不明で決定的な治療法のない、unmet medical needsの疾患である。本研究は、実際のヒト組織を用いて得た知見をもとに複雑なNASHの分子病態を明らかにしてゆく必要性を示し、診断・治療薬の開発への道を開く情報を提供する。