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Increased LHX9 expression in alveolar epithelial type 2 cells of patients with chronic obstructive pulmonary disease

Research Project

Project/Area Number 18K08134
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 InstitutionTohoku University

Principal Investigator

Yamada Mitsuhiro  東北大学, 大学病院, 講師 (00396483)

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: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsCOPD
Outline of Final Research Achievements

Although we previously reported that LHX9 mRNA expression was up-regulated in AT2 cells of COPD lung tissues, it is yet to be elucidated how LHX9 is associated with the vulnerability of AT2 cells in COPD. In this study, we revealed that LHX9 mRNA expression was increased in AT2 cells from COPD lung tissues, compared to non-COPD. The airflow obstruction was independently correlated with the increase in LHX9 expression. Among several pro-inflammatory cytokines, interferon-γ was a strong inducer for LHX9 expression in A549 cells. Lhx9 was involved in the increased susceptibility to serum starvation-induced cell death of A549 cells. Our data suggest that IFN-γ predominantly increases the LHX9 expression which enhances the susceptibility to cell death. Considering the independent association of the increased LHX9 expression in AT2 cells with airflow obstruction, the IFN-γ-Lhx9 axis might contribute to the vulnerability of AT2 cells in the lungs of COPD.

Academic Significance and Societal Importance of the Research Achievements

本研究はLHX9によるⅡ型細胞の機能制御がCOPD病態の形成に重要な役割を持っている可能性を示唆した。現在行われているCOPDに対する治療は、気管支拡張薬やテオフィリン製剤を用いた気流閉塞の解除が主体であり、気道・肺組織のリモデリング制御等、根本的な治療は開発されていない。本研究結果から、COPDのⅡ型細胞の脆弱性にはIFNγ-LHX9シグナル伝達経路が関与している可能性が示唆されたが、COPDにおいてこの経路を抑制することで、COPD肺組織においてⅡ型細胞の幹細胞活性を維持できる可能性がある。このことは、現在世界中の脅威となっているCOVID-19肺炎の重症化阻止にも役立つ可能性がある。

Report

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

    (14 results)

All 2021 2020 2019 2018

All Journal Article (12 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 12 results,  Open Access: 12 results) Presentation (2 results) (of which Invited: 2 results)

  • [Journal Article] PGC-1α regulates airway epithelial barrier dysfunction induced by house dust mite2021

    • Author(s)
      Saito Tsutomu、Ichikawa Tomohiro、Numakura Tadahisa、Yamada Mitsuhiro、Koarai Akira、Fujino Naoya、Murakami Koji、Yamanaka Shun、Sasaki Yusaku、Kyogoku Yorihiko、Itakura Koji、Sano Hirohito、Takita Katsuya、Tanaka Rie、Tamada Tsutomu、Ichinose Masakazu、Sugiura Hisatoshi
    • Journal Title

      Respiratory Research

      Volume: 22 Issue: 1 Pages: 63-63

    • DOI

      10.1186/s12931-021-01663-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extracellular vesicles: Their emerging roles in the pathogenesis of respiratory diseases2021

    • Author(s)
      Yamada Mitsuhiro
    • Journal Title

      Respiratory Investigation

      Volume: - Issue: 3 Pages: 302-311

    • DOI

      10.1016/j.resinv.2021.02.006

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Roles of MicroRNAs and Extracellular Vesicles in the Pathogeneses of Idiopathic Pulmonary Fibrosis and Acute Respiratory Distress Syndrome2020

    • Author(s)
      Yamada Mitsuhiro
    • Journal Title

      The Tohoku Journal of Experimental Medicine

      Volume: 251 Issue: 4 Pages: 313-326

    • DOI

      10.1620/tjem.251.313

    • NAID

      130007885669

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Treatment with LABA versus LAMA for stable COPD: a systematic review and meta-analysis.2020

    • Author(s)
      Koarai A, Sugiura H, Yamada M, Ichikawa T, Fujino N, Kawayama T, Ichinose M.
    • Journal Title

      BMC Pulm Med

      Volume: 20 Issue: 1 Pages: 111-111

    • DOI

      10.1186/s12890-020-1152-8

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Decreased expression of a phagocytic receptor Siglec-1 on alveolar macrophages in chronic obstructive pulmonary disease2020

    • Author(s)
      Tanno Atsushi、Fujino Naoya、Yamada Mitsuhiro、Sugiura Hisatoshi、Hirano Taizou、Tanaka Rie、Sano Hirohito、Suzuki Satoshi、Okada Yoshinori、Ichinose Masakazu
    • Journal Title

      Respiratory Research

      Volume: 21 Issue: 1 Pages: 30-30

    • DOI

      10.1186/s12931-020-1297-2

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nitrosative stress in patients with asthma?chronic obstructive pulmonary disease overlap2019

    • Author(s)
      Kyogoku Yorihiko、Sugiura Hisatoshi、Ichikawa Tomohiro、Numakura Tadahisa、Koarai Akira、Yamada Mitsuhiro、Fujino Naoya、Tojo Yutaka、Onodera Katsuhiro、Tanaka Rie、Sato Kei、Sano Hirohito、Yamanaka Shun、Itakura Koji、Mitsune Ayumi、Tamada Tsutomu、Akaike Takaaki、Ichinose Masakazu
    • Journal Title

      Journal of Allergy and Clinical Immunology

      Volume: 144 Issue: 4 Pages: 972-983

    • DOI

      10.1016/j.jaci.2019.04.023

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Increase in circulating ACE-positive endothelial microparticles during acute lung injury2019

    • Author(s)
      Takei Yusuke、Yamada Mitsuhiro、Saito Koji、Kameyama Yoshinobu、Sugiura Hisatoshi、Makiguchi Tomonori、Fujino Naoya、Koarai Akira、Toyama Hiroaki、Saito Kazutomo、Ejima Yutaka、Kawazoe Yu、Kudo Daisuke、Kushimoto Shigeki、Yamauchi Masanori、Ichinose Masakazu
    • Journal Title

      European Respiratory Journal

      Volume: 54 Issue: 4 Pages: 1801188-1801188

    • DOI

      10.1183/13993003.01188-2018

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sensing of apoptotic cells through Axl causes lung basal cell proliferation in inflammatory diseases2019

    • Author(s)
      Fujino Naoya、Brand Oliver J.、Morgan David J.、Fujimori Toshifumi、Grabiec Aleksander M.、Jagger Christopher P.、Maciewicz Rose A.、Yamada Mitsuhiro、Itakura Koji、Sugiura Hisatoshi、Ichinose Masakazu、Hussell Tracy
    • Journal Title

      Journal of Experimental Medicine

      Volume: 216 Issue: 9 Pages: 2184-2201

    • DOI

      10.1084/jem.20171978

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Axl kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas2019

    • Author(s)
      Tsukita Yoko、Fujino Naoya、Miyauchi Eisaku、Saito Ryoko、Fujishima Fumiyoshi、Itakura Koji、Kyogoku Yorihiko、Okutomo Koji、Yamada Mitsuhiro、Okazaki Tatsuma、Sugiura Hisatoshi、Inoue Akira、Okada Yoshinori、Ichinose Masakazu
    • Journal Title

      Molecular Cancer

      Volume: 18 Issue: 1 Pages: 24-24

    • DOI

      10.1186/s12943-019-0953-y

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Improving the viability of tissue‐resident stem cells using an organ‐preservation solution2019

    • Author(s)
      Suzuki Takaya、Ota Chiharu、Fujino Naoya、Tando Yukiko、Suzuki Satoshi、Yamada Mitsuhiro、Kondo Takashi、Okada Yoshinori、Kubo Hiroshi
    • Journal Title

      FEBS Open Bio

      Volume: 9 Issue: 12 Pages: 2093-2104

    • DOI

      10.1002/2211-5463.12748

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The cholinergic anti-inflammatory pathway: an innovative treatment strategy for respiratory diseases and their comorbidities2018

    • Author(s)
      Yamada Mitsuhiro、Ichinose Masakazu
    • Journal Title

      Current opinion in pharmacology

      Volume: 40 Pages: 18-25

    • DOI

      10.1016/j.coph.2017.12.003

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Cholinergic Pathways in Inflammation: A Potential Pharmacotherapeutic Target for COPD2018

    • Author(s)
      Yamada Mitsuhiro、Ichinose Masakazu
    • Journal Title

      Frontiers in Pharmacology

      Volume: 9 Pages: 1426-1426

    • DOI

      10.3389/fphar.2018.01426

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 異種細胞間コミュニケーションに着目した難治性呼吸器疾患の病態解明とバイオマーカー探索2020

    • Author(s)
      山田充啓
    • Organizer
      第60回日本呼吸器学会学術講演会 令和元年度 熊谷賞受賞講演
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 肺組織修復のメカニズム 細胞治療の可能性2019

    • Author(s)
      山田 充啓
    • Organizer
      第59回日本呼吸器学会学術講演会
    • Related Report
      2019 Research-status Report
    • Invited

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

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