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Development of a novel therapy for interstitial lung disease focused on histidine-rich glycoprotein

Research Project

Project/Area Number 20K17747
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 55040:Respiratory surgery-related
Research InstitutionOkayama University

Principal Investigator

Shiotani Toshio  岡山大学, 医学部, 客員研究員 (90851246)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords高ヒスチジン糖タンパク質(HRG) / 間質性肺炎 / 肺移植 / 原発性移植片機能不全(PGD)) / バイオマーカー / 新規治療法 / 虚血再灌流障害(IRI) / 肺線維症(IPF) / 原発性移植片機能不全(PGD) / 新規治療 / 肺線維症 / ブレオマイシン / 高ヒスチジン糖タンパク質 / 早期移植肺機能不全 / 慢性肺移植片機能不全 / 肺障害
Outline of Research at the Start

肺線維化は慢性炎症により、様々な炎症関連分子が関与することが報告されている。
当施設では炎症性サイトカインを抑制する、高ヒスチジン糖タンパク質(Histidinerich glycoprotein, HRG)の研究を精力的に行っており、HRGがTNF-α・IL-6の発現を抑制するという知見を得た。この知見にヒントを得て「抗炎症タンパク質であるHRGが肺の線維化を抑制する」という仮説を立てた。本研究では、HRG-TNF-α・IL-6-miR21-TGF-βの分子シークエンスに着目し、線維化をきたす肺疾患に対する新規治療法の開発を目指す。

Outline of Final Research Achievements

In this study, we first measured plasma levels of histidine-rich glycoprotein (HRG) in patients with idiopathic pulmonary fibrosis (IPF). Second, plasma HRG levels were measured in primary graft dysfunction (PGD) after lung transplantation. Finally, plasma HRG levels were measured in acute lung injury using a mouse model of ischemia-reperfusion injury. Plasma HRG levels were decreased in IPF and PGD patients, and plasma HRG levels were also decreased in the mouse IRI model, suggesting that supplemental HRG therapy may be a new therapeutic strategy in acute and chronic lung injury.

Academic Significance and Societal Importance of the Research Achievements

間質性肺炎は慢性炎症による肺疾患の一つであり、現在TGF-β等を標的とした抗線維化薬をはじめ、複数の薬剤による治療が行われるが、その治療法は確立しておらず、肺線維化を引き起こす経路を標的とした治療法の確立が急務とされている。また、間質性肺炎の最終的な治療として肺移植が行われるが、肺移植後の原発性移植片機能不全は、肺移植後に発症する急性肺障害であり、肺移植の予後を妨げる一因となっている。本研究成果により、高ヒスチジン糖タンパク質の補充療法が間質性肺炎や原発性移植片機能不全の新規治療法として応用できる可能性がある。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (5 results)

All 2023 2021

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Diagnostic value of circulating microRNA-21 in chronic lung allograft dysfunction after bilateral cadaveric and living-donor lobar lung transplantation2023

    • Author(s)
      Shiotani Toshio、Sugimoto Seiichiro、Tomioka Yasuaki、Yamamoto Haruchika、Tanaka Shin、Miyoshi Kentaroh、Suzawa Ken、Shien Kazuhiko、Yamamoto Hiromasa、Okazaki Mikio、Toyooka Shinichi
    • Journal Title

      Heliyon

      Volume: 9 Issue: 4 Pages: e14903-e14903

    • DOI

      10.1016/j.heliyon.2023.e14903

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Emphysematous changes and lower levels of plasma irisin are associated with bronchiolitis obliterans syndrome after bilateral living-donor lobar lung transplantation2021

    • Author(s)
      Shiotani Toshio、Sugimoto Seiichiro、Yamamoto Haruchika、Miyoshi Kentaroh、Otani Shinji、Suzawa Ken、Yamamoto Hiromasa、Okazaki Mikio、Yamane Masaomi、Toyooka Shinichi
    • Journal Title

      Surgery Today

      Volume: 52 Issue: 2 Pages: 294-305

    • DOI

      10.1007/s00595-021-02339-w

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Long-term Follow-up of Living-Donor Kidney Transplantation after Cadaveric Lung Transplantation2021

    • Author(s)
      Toshio Shiotani, Seiichiro Sugimoto, Kota Araki, Yasuaki Tomioka, Kentaroh Miyoshi, Shinji Otani, Masaomi Yamane, Shinichi Toyooka
    • Journal Title

      Acta Medica Okayama

      Volume: 75 Pages: 87-89

    • NAID

      120006980487

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-term Follow-up of Living-Donor Kidney Transplantation after Cadaveric Lung Transplantation2021

    • Author(s)
      Shiotani T, Sugimoto S, Araki K, Tomioka Y, Miyoshi K, Otani S, Yamane M, Toyooka S.
    • Journal Title

      Acta Medica Okayama

      Volume: 75 Issue: 1 Pages: 87-89

    • DOI

      10.18926/AMO/61439

    • NAID

      120006980487

    • URL

      https://ousar.lib.okayama-u.ac.jp/61439

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Plasma Levels of Histidine-Rich Glycoprotein are Associated with the Development of Primary Graft Dysfunction after Lung Transplantation2021

    • Author(s)
      Shiotani Toshio、Sugimoto Seiichiro、Yamamoto Haruchika、Matubara Kei、Shimizu Dai、Nakata Kentaro、Tomioka Yasuaki、Miyoshi Kentaroh、Otani Shinji、Okazaki Mikio、Yamane Masaomi、Toyooka Shinichi
    • Organizer
      The International Society for Heart and Lung Transplantation 41nd Annual Meeting & Scientific Sessions
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research

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Published: 2020-04-28   Modified: 2024-01-30  

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