Role of Mieap in COPD pathogenesis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08578
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Wakui Hiroshi 東京慈恵会医科大学, 医学部, 講師 (10773533)
• Co-Investigator(Kenkyū-buntansha): 荒屋 潤 東京慈恵会医科大学, 医学部, 教授 (90468679)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 慢性閉塞性肺疾患 / 細胞老化 / Mieap / ミトコンドリア

Outline of Final Research Achievements

Mitochondria-eating protein (Mieap) is induced in a p53-dependent manner and affects mitochondrial homeostasis. In this study, we found that Mieap expression was decreased in lung and airway epithelial cells from patients with chronic obstructive pulmonary disease (COPD). Cigarette smoke extract (CSE) induced Mieap expression in airway epithelial cells, which was involved in the regulation of mitochondrial electron-transfer homeostasis, mitochondrial ROS production, and cellular senescence. Mieap knockout mice showed increased inflammation and cellular senescence accompanied by worsened emphysema-like lesion development. It is likely that reduced Mieap expression is involved in the COPD pathogenesis through enhancing cellular senescence.

Free Research Field

呼吸器病学

Academic Significance and Societal Importance of the Research Achievements

加齢関連疾患であるCOPDは、細胞老化の亢進が病態に関与する、治療抵抗性呼吸器疾患である。今回MieapのCOPDへの関与が、細胞老化の制御の点から示されたことは、病態解明だけでなく、新規治療法開発のための手掛かりになると考えられる。