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

Exploring treatments based on a new understanding of the pathogenesis of pulmonary fibrosis.

Research Project

Project/Area Number 21K16118
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionOsaka University

Principal Investigator

Fukushima Kiyoharu  大阪大学, 免疫学フロンティア研究センター, 特任助教(常勤) (00752156)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2023: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2022: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords肺線維症 / 単球 / 線維症 / 動物モデル
Outline of Research at the Start

特発性肺線維症(IPF)は、予後不良の指定難病であり, 根治薬も存在しない。申請者らはマウス肺線維症モデルにおいて免疫細胞における線維化促進性単球サブセットを報告し(Nature 2017), 続いて, 非免疫細胞において線維化期に誘導されるRBM7という遺伝子が, NEAT1というlong non-coding RNAの分解を介して線維症の発症に関与していることを解明した. (Immunity 2020).本研究では、先行する肺線維症研究を発展させ、マウスモデルを有効活用しながら, ヒト肺線維症において新たな病態理解に基づく治療標的の確立を目指す。

Outline of Final Research Achievements

Idiopathic pulmonary fibrosis (IPF) is an incurable disease with a poor prognosis and a strong association with smoking in its pathogenesis. We aim to gain a comprehensive understanding of the pathogenesis of fibrosis by investigating the mechanisms of fibrosis regulation by the RBM7/NEAT1/CXCL12 cascade and the interplay between immune and non-immune cells, as identified in previous studies. The regulatory mechanisms of RBM7 expression were investigated. The novel pathogenesis of fibrotic lesions was investigated by single-cell RNA-seq analysis of lung fibrosis patient samples. Advanced fibrotic lung is considered a devastating end-stage disease, but an active immune response has been shown to maintain fibroblast activation and promote fibrosis. By studying the mechanisms of fibrosis regulation through the interplay between immune and non-immune cells, we have been able to elucidate the molecular and intercellular dynamics that maintain and promote fibrosi

Academic Significance and Societal Importance of the Research Achievements

今なお根本的な治療薬は開発されておらず、効果的な治療法が不足しているIPFに対して、申請者のグループはSatMやRBM7等の新たな知見を次々に見いだして報告してきており、これらの新知見により肺線維症の発症メカニズムの理解に関して大きな転換がもたらされた。
本研究は、申請者の新知見によりもたらされた肺線維症発症のメカニズムに基づく病態理解をさらに発展させるものであり、社会的にも求められる方向性であり、本研究により線維症を引き起こすメカニズムを新たな視点から理解することが出来るとともに、本研究により新たに見出される知見は更なる新規治療への応用が期待できる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (16 results)

All 2024 2023 2022 2021

All Journal Article (14 results) (of which Peer Reviewed: 14 results,  Open Access: 11 results) Presentation (2 results)

  • [Journal Article] MGIT-seq for the Identification of Nontuberculous Mycobacteria and Drug Resistance: a Prospective Study2023

    • Author(s)
      Fukushima K、Matsumoto Y、Matsuki T、Saito H、Motooka D、Komukai S、Fukui E、Yamuchi J、Nitta T、Niitsu T、Abe Y、Nabeshima H、Nagahama Y、Nii T、Tsujino K、Miki K、Kitada S、Kumanogoh A、Akira S、Nakamura S、Kida H
    • Journal Title

      Journal of Clinical Microbiology

      Volume: 61 Issue: 4

    • DOI

      10.1128/jcm.01626-22

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Invariant natural killer T cells and iron metabolism orchestrate skin development and homeostasis2023

    • Author(s)
      Nabeshima H, Niitsu T, Fukushima K, Kida H
    • Journal Title

      Cellular & Molecular Immunology

      Volume: 20 Issue: 10 Pages: 1095-1097

    • DOI

      10.1038/s41423-023-01016-x

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identifying phenotypes in interstitial lung disease using group-based trajectory modelling2023

    • Author(s)
      Takata S.、Komukai S.、Hoshino T.、Tabuchi H.、Masuhiro K.、Yaga M.、Shirai Y.、Mitsui Y.、Abe Y.、Kuge T.、Fukushima K.、Kida H.、Kumanogoh A.
    • Journal Title

      The International Journal of Tuberculosis and Lung Disease

      Volume: 27 Issue: 4 Pages: 332-334

    • DOI

      10.5588/ijtld.22.0417

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Real-world impact of antifibrotics on prognosis in patients with progressive fibrosing interstitial lung disease2023

    • Author(s)
      Niitsu Takayuki、Fukushima Kiyoharu、Komukai Sho、Takata So、Abe Yuko、Nii Takuro、Kuge Tomoki、Iwakoshi Shinichi、Shiroyama Takayuki、Miyake Kotaro、Tujino Kazuyuki、Tanizaki Satoshi、Iwahori Kota、Hirata Haruhiko、Miki Keisuke、Yanagawa Masahiro、Takeuchi Noriyuki、Takeda Yoshito、Kida Hiroshi、Kumanogoh Atsushi
    • Journal Title

      RMD Open

      Volume: 9 Issue: 1 Pages: e002667-e002667

    • DOI

      10.1136/rmdopen-2022-002667

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chronic Pulmonary Disease Caused by <i>Tsukamurella toyonakaense</i>2022

    • Author(s)
      Kuge Tomoki、Fukushima Kiyoharu、Matsumoto Yuki、Saito Haruko、Abe Yuko、Akiba Eri、Haduki Kako、Nitta Tadayoshi、Kawano Akira、Tanaka Michio、Hattori Yumi、Kawasaki Takahiro、Matsuki Takanori、Shiroyama Takayuki、Motooka Daisuke、Tsujino Kazuyuki、Miki Keisuke、Mori Masahide、Kitada Seigo、Nakamura Shota、etc
    • Journal Title

      Emerging Infectious Diseases

      Volume: 28 Issue: 7 Pages: 1437-1441

    • DOI

      10.3201/eid2807.212320

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mycobacterium senriense sp. nov., a slowly growing, non-scotochromogenic species, isolated from sputum of an elderly man2022

    • Author(s)
      Abe Yuko、Fukushima Kiyoharu、Matsumoto Yuki、Niitsu Takayuki、Nabeshima Hiroshi、Nagahama Yasuharu、Akiba Eri、Haduki Kako、Saito Haruko、Nitta Tadayoshi、Kawano Akira、Tanaka Michio、Matsuki Takanori、Motooka Daisuke、Tsujino Kazuyuki、Miki Keisuke、Nakamura Shota、Iida Tetsuya、Kida Hiroshi
    • Journal Title

      International Journal of Systematic and Evolutionary Microbiology

      Volume: 72 Issue: 5 Pages: 005378-005378

    • DOI

      10.1099/ijsem.0.005378

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Specific targeting of lung ILC2s via NRP1 in pulmonary fibrosis2022

    • Author(s)
      Nii Takuro、Fukushima Kiyoharu、Kida Hiroshi
    • Journal Title

      Cellular &amp; Molecular Immunology

      Volume: 19 Issue: 8 Pages: 869-871

    • DOI

      10.1038/s41423-022-00867-0

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Diagnosis of Nontuberculous Mycobacterial Pulmonary Disease by Single Bacterial Isolation Plus Anti-GPL-Core IgA Antibody2022

    • Author(s)
      Kawasaki Takahiro、Kitada Seigo、Fukushima Kiyoharu、Akiba Eri、Haduki Kako、Saito Haruko、Nitta Tadayoshi、Kawano Akira、Miyazaki Akito、Nii Takuro、Kuge Tomoki、Koba Taro、Matsuki Takanori、Tsujino Kazuyuki、Miki Keisuke、Maekura Ryoji、Kida Hiroshi
    • Journal Title

      Microbiology Spectrum

      Volume: 10 Issue: 1

    • DOI

      10.1128/spectrum.01406-21

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fatal cytomegalovirus pneumonia in a critically ill patient with <scp>COVID</scp> ‐192021

    • Author(s)
      Amiya Saori、Hirata Haruhiko、Shiroyama Takayuki、Adachi Yuichi、Niitsu Takayuki、Noda Yoshimi、Enomoto Takatoshi、Hara Reina、Fukushima Kiyoharu、Suga Yasuhiko、Miyake Kotaro、Koide Moe、Uchiyama Akinori、Takeda Yoshito、Kumanogoh Atsushi
    • Journal Title

      Respirology Case Reports

      Volume: 9 Issue: 7

    • DOI

      10.1002/rcr2.801

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pleural Effusion Caused by Mycolicibacterium mageritense in an Immunocompetent Host: A Case Report2021

    • Author(s)
      Niitsu Takayuki、Kuge Tomoki、Fukushima Kiyoharu、Matsumoto Yuki、Abe Yuko、Okamoto Masashi、Haduki Kako、Saito Haruko、Nitta Tadayoshi、Kawano Akira、Matsuki Takanori、Motooka Daisuke、Tsujino Kazuyuki、Miki Keisuke、Nakamura Shota、Kida Hiroshi、Kumanogoh Atsushi
    • Journal Title

      Frontiers in Medicine

      Volume: 8

    • DOI

      10.3389/fmed.2021.797171

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Loss of FCHSD1 leads to amelioration of chronic obstructive pulmonary disease2021

    • Author(s)
      Kawasaki Takahiro、Sugihara Fuminori、Fukushima Kiyoharu、Matsuki Takanori、Nabeshima Hiroshi、Machida Tomohisa、Mitsui Yuichi、Fujimura Saki、Sagawa Rio、Gaheun Lee、Kuniyoshi Kanako、Tanaka Hiroki、Narazaki Masashi、Kumanogoh Atsushi、Akira Shizuo、Satoh Takashi
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 118 Issue: 26

    • DOI

      10.1073/pnas.2019167118

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Serum GPL core antibody levels are associated with disease activity and treatment outcomes in Mycobacterium avium complex lung disease following first line antibiotic treatment2021

    • Author(s)
      Fukushima Kiyoharu、Kitada Seigo、Matsumoto Yuki、Komukai Sho、Kuge Tomoki、Kawasaki Takahiro、Matsuki Takanori、Motooka Daisuke、Tsujino Kazuyuki、Miki Mari、Miki Keisuke、Nakamura Shota、Kida Hiroshi
    • Journal Title

      Respiratory Medicine

      Volume: 187 Pages: 106585-106585

    • DOI

      10.1016/j.rmed.2021.106585

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Advances and Challenges of Antibody Therapeutics for Severe Bronchial Asthma2021

    • Author(s)
      Abe Yuko、Suga Yasuhiko、Fukushima Kiyoharu、Ohata Hayase、Niitsu Takayuki、Nabeshima Hiroshi、Nagahama Yasuharu、Kida Hiroshi、Kumanogoh Atsushi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 1 Pages: 83-83

    • DOI

      10.3390/ijms23010083

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel insights into the pathogenesis of lung fibrosis: the RBM7?NEAT1?CXCL12?SatM axis at fibrosis onset2021

    • Author(s)
      Fukushima Kiyoharu、Akira Shizuo
    • Journal Title

      International Immunology

      Volume: 33 Issue: 12 Pages: 659-663

    • DOI

      10.1093/intimm/dxab034

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 空間・細胞間ダイナミズムから導く進行性線維化の新たな病態理解2024

    • Author(s)
      福島 清春
    • Organizer
      第64回 日本呼吸器学会学術講演会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 新規線維症関連遺伝子RBM7によるnon-coding RNA分解を介する線維化制御2021

    • Author(s)
      福島清春、佐藤荘、熊ノ郷淳、審良静男
    • Organizer
      第61回呼吸器学会学術講演会
    • Related Report
      2021 Research-status Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi