Intracellular communication mediated by exosomal micro RNA in aging-related lung diseases

• Project/Area Number: 15K09232
• 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: Kuwano Kazuyoshi 東京慈恵会医科大学, 医学部, 教授 (40205266)
• Co-Investigator(Kenkyū-buntansha): 荒屋 潤 東京慈恵会医科大学, 医学部, 講師 (90468679)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 細胞老化 / ミトコンドリア / エクソソーム / 慢性閉塞性肺疾患 / 特発性肺線維症 / マイクロＲＮＡ / オートファジー / microRNA / 気道上皮細胞 / 繊維芽細胞 / マイクロRNA

Outline of Final Research Achievements

COPD and IPF are chronically progressive and lethal lung diseases. Extracellular vesicles (EVs), including exosome and microvesicle, are recognized as important mediators of intercellular communication. We investigated the involvement of EV-mediated intercellular communication between lung fibroblasts (LFs) and human bronchial epithelial cells (HBECs) in COPD and IPF pathogenesis. We confirmed that they were internalized when incubated with HBECs or fibroblasts.Cigarette smoking extracts (CSE) induced cellular senescence in HBEC. EVs derived from senescent HBEC induced myofibroblast differentiation. We identified miR210 in exosome deribed from senescent HBEC as an effector miRNA. EVs derived from IPF-LFs induced mitochondrial dysfunction and ROS accompanied by cellular senescence in HBECs. Three upregulated EV miRNAs from IPF-LF regulated cellular senescence and mitochondrial dysfunction via targeting SIRT3 in HBEC.

Research Products

• [Journal Article] Suppression of autophagy by extracellular vesicles promotes myofibroblast differentiation in COPD pathogenesis. (2015)
  • Author(s): Fujita Y, Araya J, Ito S, Kobayashi K, Kosaka N, Yoshioka Y, Kadota T, Hara H, Kuwano K, Ochiya T.
  • Journal Title: J Extracell Vesicles Volume: 4 Issue: 1 Pages: 28388-28399
  • DOI: 10.3402/jev.v4.28388
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Myofibroblasts derived extracellular vesicles promotes epithelial cell senescence in idiopathic pulmonary fibrosis. (2017)
  • Author(s): 3.Tsukasa Kadota, Yusuke Yoshioka, Yu Fujita, Jun Araya, Kazuyoshi Kuwano, Takahiro Ochiya
  • Organizer: ISEV2017Annual Meeting
  • Int'l Joint Research