Epigenetic regulation of chronic inflammation by metabolic stress

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09038
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Keio University (2020-2022); Tokyo Metropolitan Children's Medical Center (Department of Clinical Research) (2019)
• Principal Investigator: HACHIYA Rumi 慶應義塾大学, 医学部(信濃町), 共同研究員 (50365318)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 慢性炎症 / エピジェネティクス / マクロファージ / 肥満

Outline of Final Research Achievements

We have demonstrated that SET domain, bifurcated 1 (Setdb1) in macrophages potently suppresses Toll-like receptor 4 (TLR4)-mediated expression of proinflammatory cytokines which is stimulated by lipopolysaccharide. In this study our aim was to clarify the role of Setdb1 in chronic inflammation by metabolic stress which is related to obese adipose tissue inflammation. We made Setdb1 knock-down macrophage cell line and demonstrated that Setdb1 suppresses inflammation by saturated fatty acid. Moreover, we identified the factors which is regulated by Setdb1 by in silico analysis.

Free Research Field

小児科学、内分泌学

Academic Significance and Societal Importance of the Research Achievements

本研究課題の学術的意義は、いまだに知見の少ないマクロファージの炎症におけるエピジェネティック制御機構にアプローチしている点にある。社会的意義は、炎症性サイトカイン発現を抑制するエピジェネティック分子であるSetdb1が、飽和脂肪酸による慢性炎症の治療標的としての可能性が期待できる点にある。