Role of mitophagy in inflammasome activation during COPD pathogenesis.

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461198
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Shimizu Kenichiro 東京慈恵会医科大学, 医学部, 助教 (80385327)
• Co-Investigator(Kenkyū-buntansha): ARAYA JUN 東京慈恵会医科大学, 医学部, 准教授 (90468679)
• Co-Investigator(Renkei-kenkyūsha): KUWANO KAZUYOSHI 東京慈恵会医科大学, 医学部, 教授 (40205266)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: インフラマソーム / 慢性閉塞性肺疾患 / マイトファジー

Outline of Final Research Achievements

Cigarette smoke accelerates epithelial cell senescence in the lung, which has been implicated in COPD pathogenesis. Cigarette smoke extract (CSE) induces mitochondrial damage and ROS production, resulting in inflammasome activation and cellular senescence in human bronchial epithelial cell (HBEC). Mitophagy, a mechanism for maintaining cellular homeostasis by removing damaged mitochondria, is induced by CSE exposure. CSE-induced mitophagy is inhibited by PARK2 kockdown with concomitantly enhanced mitochondrial ROS production and cellular senescence. Inversely, PARK2 overexpression inhibits CSE-induced ROS production and cellular senescence. PARK2 expression levels are decreased in COPD lungs compared with non-COPD lungs. Insufficient mitophagy is a part of the pathogenic sequence of COPD development via increased ROS production, resulting from accumulation of damaged mitochondria.

Free Research Field

医歯薬学