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Establishment of an Asthma-COPD Overlap (ACO) Mouse Model Using Papain

Research Project

Project/Area Number 18K15946
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionThe University of Tokyo

Principal Investigator

Hiraishi Yoshihisa  東京大学, 医学部附属病院, 届出研究員 (90783514)

Project Period (FY) 2018-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
KeywordsACO / 喘息 / COPD / 気管支喘息 / マウスモデル / パパイン(papain) / papain / プロテアーゼ
Outline of Final Research Achievements

We focused on papain, a cysteine protease from the plant papaya, as an animal model that conveniently reproduces the clinical features of ACO. We compared a pig pancreatic elastase (PPE)-induced COPD model and a PBS-treated group with a model in which papain was repeatedly administered. In the lung pathology of each group, emphysema formation was observed in the PPE and papain groups. Eosinophils in bronchoalveolar lavage fluid were significantly increased in the repeated papain-treated mice compared to the other groups, and in the airway hyperresponsiveness test to methacholine inhalation, the papain group showed significantly increased airway hyperresponsiveness and asthmatic features. Repeated papain-treated mice were shown to be a reasonable model for human ACO.

Academic Significance and Societal Importance of the Research Achievements

喘息・COPDオーバーラップ(ACO)については、重要な呼吸器疾患である一方、背景病態の理解はいまだ未解明である。本モデルは、小動物を用いて簡便に作成できる一方、COPDおよびヒト気管支喘息に相当する特徴も有することが示された。前述の通りヒトCOPDとしての特徴を持つことも合わせ、本研究におけるパパイン反復投与マウスはヒトACOを模したモデルとして妥当であると示された。

Report

(7 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (12 results)

All 2024 2023 2022 2020 2019 2018

All Journal Article (11 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 11 results,  Open Access: 8 results) Presentation (1 results)

  • [Journal Article] Anti-Inflammatory Effects of Japanese Herbal Medicine Hochuekkito in a Mouse Model of Acute Exacerbation of Chronic Obstructive Pulmonary Disease2024

    • Author(s)
      Fukuda Kensuke、Matsuzaki Hirotaka、Hiraishi Yoshihisa、Miyashita Naoya、Ishii Takashi、Yuki Masaaki、Isago Hideaki、Tamiya Hiroyuki、Mitani Akihisa、Saito Akira、Jo Taisuke、Nagase Takahide
    • Journal Title

      Pharmacology

      Volume: 109 Issue: 2 Pages: 121-126

    • DOI

      10.1159/000536348

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Repeated photodynamic therapy mediates the abscopal effect through multiple innate and adaptive immune responses with and without immune checkpoint therapy.2023

    • Author(s)
      Lou J, Aragaki M, Bernards N, Chee T, Gregor A, Hiraishi Y, Ishiwata T, Leung C, Ding L, Kitazawa S, Koga T, Sata Y, Ogawa H, Chen J, Kato T, Yasufuku K, Zheng G.
    • Journal Title

      Biomaterials.

      Volume: 292 Pages: 121918-121918

    • DOI

      10.1016/j.biomaterials.2022.121918

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Preclinical feasibility of bronchoscopic fluorescence-guided lung sentinel lymph node mapping2023

    • Author(s)
      Gregor Alexander、Sata Yuki、Hiraishi Yoshihisa、Ishiwata Tsukasa、Aragaki Masato、Kitazawa Shinsuke、Koga Takamasa、Ogawa Hiroyuki、Bernards Nicholas、Yasufuku Kazuhiro
    • Journal Title

      The Journal of Thoracic and Cardiovascular Surgery

      Volume: 165 Issue: 1 Pages: 337-350

    • DOI

      10.1016/j.jtcvs.2022.08.031

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Transbronchial real-time lung tumor localization with folate receptor?targeted near-infrared molecular imaging: A proof of concept study in animal models2022

    • Author(s)
      Ishiwata Tsukasa、Hiraishi Yoshihisa、Bernards Nicholas、Sata Yuki、Gregor Alexander、Aragaki Masato、Yasufuku Kazuhiro
    • Journal Title

      The Journal of Thoracic and Cardiovascular Surgery

      Volume: - Issue: 6 Pages: 01034-0

    • DOI

      10.1016/j.jtcvs.2022.09.042

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A mouse model of asthma‐chronic obstructive pulmonary disease overlap induced by intratracheal papain2020

    • Author(s)
      Fukuda Kensuke、Matsuzaki Hirotaka、Mikami Yu、Makita Kosuke、Miyakawa Kazuko、Miyashita Naoya、Hosoki Keisuke、Ishii Takashi、Noguchi Satoshi、Urushiyama Hirokazu、Horie Masafumi、Mitani Akihisa、Yamauchi Yasuhiro、Shimura Eri、Nakae Susumu、Saito Akira、Nagase Takahide、Hiraishi Yoshihisa
    • Journal Title

      Allergy

      Volume: 76 Issue: 1 Pages: 390-394

    • DOI

      10.1111/all.14528

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhaled corticosteroid withdrawal may improve outcomes in elderly patients with COPD exacerbation: a nationwide database study2020

    • Author(s)
      Jo Taisuke、Yasunaga Hideo、Yamauchi Yasuhiro、Mitani Akihisa、Hiraishi Yoshihisa、Hasegawa Wakae、Sakamoto Yukiyo、Matsui Hiroki、Fushimi Kiyohide、Nagase Takahide
    • Journal Title

      ERJ Open Research

      Volume: 6 Issue: 1 Pages: 00246-2019

    • DOI

      10.1183/23120541.00246-2019

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Small lung tumor biopsy samples are feasible for high quality targeted next generation sequencing2019

    • Author(s)
      Kage Hidenori、Kohsaka Shinji、Shinozaki‐Ushiku Aya、Hiraishi Yoshihisa、Sato Jiro、Nagayama Kazuhiro、Ushiku Tetsuo、Takai Daiya、Nakajima Jun、Miyagawa Kiyoshi、Aburatani Hiroyuki、Mano Hiroyuki、Nagase Takahide
    • Journal Title

      Cancer Science

      Volume: 110 Issue: 8 Pages: 2652-2657

    • DOI

      10.1111/cas.14112

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Naftopidil reduced the proliferation of lung fibroblasts and bleomycin-induced lung fibrosis in mice.2019

    • Author(s)
      Urushiyama H, Terasaki Y, Nagasaka S, Kokuho N, Endo Y, Terasaki M, Kunugi S, Makita K, Isago H, Hosoki K, Souma K, Ishii T, Matsuzaki H, Hiraishi Y, Mikami Y, Noguchi S, Tamiya H, Mitani A, Yamauchi Y, Shimizu A, Nagase T.
    • Journal Title

      J Cell Mol Med.

      Volume: 3 Issue: 5 Pages: 1-9

    • DOI

      10.1111/jcmm.14255

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CISH is a negative regulator of IL-13-induced CCL26 production in lung fibroblasts2019

    • Author(s)
      Takeshima Hideyuki、Horie Masafumi、Mikami Yu、Makita Kosuke、Miyashita Naoya、Matsuzaki Hirotaka、Noguchi Satoshi、Urushiyama Hirokazu、Hiraishi Yoshihisa、Mitani Akihisa、Borok Zea、Nagase Takahide、Yamauchi Yasuhiro
    • Journal Title

      Allergology International

      Volume: 68 Issue: 1 Pages: 101-109

    • DOI

      10.1016/j.alit.2018.08.005

    • NAID

      130007557853

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] IL-33, IL-25 and TSLP contribute to development of fungal-associated protease-induced innate-type airway inflammation2018

    • Author(s)
      Hiraishi Yoshihisa、Yamaguchi Sachiko、Yoshizaki Takamichi、Nambu Aya、Shimura Eri、Takamori Ayako、Narushima Seiko、Nakanishi Wakako、Asada Yosuke、Numata Takafumi、Suzukawa Maho、Yamauchi Yasuhiro、Matsuda Akira、Arae Ken、Morita Hideaki、Hoshino Tomoaki、Suto Hajime、Okumura Ko、Matsumoto Kenji、Nakae Susumu
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 18052-18052

    • DOI

      10.1038/s41598-018-36440-x

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The roles of IL-17C in T cell-dependent and -independent inflammatory diseases2018

    • Author(s)
      Yamaguchi Sachiko、Nambu Aya、Numata Takafumi、Yoshizaki Takamichi、Narushima Seiko、Shimura Eri、Hiraishi Yoshihisa、Arae Ken、Morita Hideaki、Matsumoto Kenji、Hisatome Ichiro、Sudo Katsuko、Nakae Susumu
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 15750-15750

    • DOI

      10.1038/s41598-018-34054-x

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Characterizaton of allergic airway inflammation induced by fungal-associated proteinases2019

    • Author(s)
      Yoshihisa Hiraishi
    • Organizer
      第68回日本アレルギー学会学術大会
    • Related Report
      2019 Research-status Report 2018 Research-status Report

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Published: 2018-04-23   Modified: 2025-01-30  

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