Role of epigenomic changes and reactive sulfur species in the pathogenesis of chronic obstructive pulmonary disease

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K15453
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Tohoku University
• Principal Investigator: Sugiura Hisatoshi 東北大学, 医学系研究科, 准教授 (20445092)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: エピゲノム変化 / 活性硫黄分子種

Outline of Final Research Achievements

In the current project, we aimed to investigate the effects of epigenomic changes in lung resident cells of patients with chronic obstructive pulmonary disease (COPD). We found that the expression of CD169 in the COPD alveolar macrophages, which is involved in phagocytosis of bacteria was significantly attenuated compared to that in the control subjects. Moreover, histone in the bronchial epithelial cells from COPD patients was more nitrated compared to that from healthy subjects. In the COPD lung cells such as bronchial epithelial cells and lung fibroblasts, intracellular levels of reactive sulfur species (RSS) were significantly decreased compared to the lung cells from healthy subjects. Now, we have been studying the role of RSS producing enzyme.

Free Research Field

呼吸器内科

Academic Significance and Societal Importance of the Research Achievements

COPDにおけるエピゲノム変化が病態に及ぼす影響についてはヒストン蛋白のアセチル化の制御については解明されているが、それ以外の変化、とりわけニトロ化については全く不明である。さらに今回、明らかにした細菌貪食受容体の発現低下についてはCOPDの自然歴において重要な増悪病態と深く関連する可能性がある。活性硫黄分子種は全く新規の内因性抗酸化分子でありヒト肺に存在し、COPD患者肺においてその産生量が低下していることは世界初の知見である。本研究成果は呼吸器領域のトップジャーナルであるThorax誌に掲載された。