• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Impaired lysophagy in COPD pathogenesis.

Research Project

Project/Area Number 18K08158
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionJikei University School of Medicine

Principal Investigator

ARAYA JUN  東京慈恵会医科大学, 医学部, 教授 (90468679)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsリソファジー / 慢性閉塞性肺疾患 / 細胞老化 / リソソーム / オートファジー / Galectin3 / TRIM16 / COPD / ガレクチン3
Outline of Final Research Achievements

Cigarette smoke (CS)-induced functional deterioration of lysosomes may be associated with chronic obstructive pulmonary disease (COPD) pathogenesis. Lysosomal membrane permeabilization (LMP) is indicative of damaged lysosomes. Galectin-3 and tripartite motif proteins (TRIM)16 play a cooperative role in recognizing LMP and inducing lysophagy. TRIM16 was involved in CSE-induced lysophagy, with impaired lysophagy associated with lysosomal dysfunction and accelerated cellular senescence. Airway epithelial cells in COPD lungs showed an increase in galectin-3 puncta reflecting lysosomal damage with concomitantly reduced TRIM16 expression levels. HBEC isolated from COPD patients showed reduced TRIM16 but increased galectin-3, and a negative correlation between TRIM16 and galectin-3 protein levels was demonstrated. Increased LMP, which can be attributed to impaired TRIM16-mediated lysophagy, may be responsible for COPD pathogenesis through the enhancement of cellular senescence.

Academic Significance and Societal Importance of the Research Achievements

老化関連呼吸器疾患であるCOPDは、高齢化社会に伴いその患者数は増加し、社会的にも医療経済的にも、その病態解明と有効な治療法の開発は重要な課題である。
我々はCOPD病態における細胞老化の亢進に、リソソーム傷害の蓄積が関与することを見出した。このリソソーム傷害の機序として、TRIM16という蛋白が関与するリソソーム選択的なオートファジー分解である、リソファジーの機能低下の影響を明らかにした。
リソファジー誘導が、COPD病態の制御に有効である可能性が示されており、今後の治療法開発につながる結果と考えている。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (4 results)

All 2021 2020 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (3 results)

  • [Journal Article] Chaperone-Mediated Autophagy Suppresses Apoptosis via Regulation of the Unfolded Protein Response during Chronic Obstructive Pulmonary Disease Pathogenesis2020

    • Author(s)
      Hosaka Y、Araya J、Fujita Y、Kadota T、Tsubouchi K、Yoshida M、Minagawa S、Hara H、Kawamoto H、Watanabe N、Ito A、Ichikawa A、Saito N、Okuda K、Watanabe J、Takekoshi D、Utsumi H、Hashimoto M、Wakui H、Ito S、Numata T、Mori S、Matsudaira H、Hirano J、Ohtsuka T、Nakayama Katsutoshi、Kuwano K
    • Journal Title

      The Journal of Immunology

      Volume: 205 Issue: 5 Pages: 1256-1267

    • DOI

      10.4049/jimmunol.2000132

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] TRIM16依存性リソファジーによる喫煙刺激誘導性細胞老化の制御2021

    • Author(s)
      保坂 悠介
    • Organizer
      日本呼吸器学学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] COPD病態におけるリソファジーの役割2019

    • Author(s)
      荒屋 潤
    • Organizer
      日本呼吸器学会学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] COPD病態におけるリソファジーの役割2019

    • Author(s)
      荒屋 潤
    • Organizer
      第59回日本呼吸器学会学術講演会
    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi