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An attempt to elucidate the pathophysiology of idiopathic pulmonary fibrosis using type I alveolar epithelium-derived substance RAGE

Research Project

Project/Area Number 17K09655
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionHiroshima University

Principal Investigator

Iwamoto Hiroshi  広島大学, 医系科学研究科(医), 講師 (60457398)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords特発性肺線維症 / 間質性肺炎 / 急性増悪 / バイオマーカー / 治療薬 / RAGE / 特発性間質性肺炎 / 肺線維症 / 肺胞上皮
Outline of Final Research Achievements

HMGB1 (high mobility group box-1 protein), which is secreted extracellularly when cells are damaged, is elevated in the blood of patients with intractable disease called idiopathic pulmonary fibrosis (IPF). Moreover, IPF patients with higher HMGB1 had higher risk of acute exacerbation. esRAGE (endogenous secretory receptor for advanced glycation end product), which binds to HMGB1 and suppress its effect, is decreased in patients with IPF. Moreover, IPF patients with lower esRAGE levels had poorer survival. In mouse pneumonitis model experiment, it was found that RAGE inhibitor can be applied to the treatment of pneumonitis.

Academic Significance and Societal Importance of the Research Achievements

今回の研究結果から、難病である特発性肺線維症患者の血中HMGB1、esRAGEを測定することにより、患者の予後や急性増悪の予測、急性増悪を起こした際の予後予測など、治療の適応を判断する上で重要な疾患進行の予測出来たことから、新規の血液検査としての可能性が示された。また動物実験の結果からはこのHMGB1、RAGEが関わる分子機構が特発性肺線維症の治療にも応用できる可能性が示され、新規治療薬の開発の一歩を示した。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (17 results)

All 2020 2019 2018 2017

All Journal Article (12 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 12 results,  Open Access: 7 results) Presentation (5 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Serum high-mobility group box 1 is associated with the onset and severity of acute exacerbation of idiopathic pulmonary fibrosis.2020

    • Author(s)
      Yamaguchi K, Iwamoto H, Sakamoto S, Horimasu Y, Masuda T, Miyamoto S, Nakashima T, Ohshimo S, Fujitaka K, Hamada H, Hattori N.
    • Journal Title

      Respirology.

      Volume: 25 Issue: 3 Pages: 275-280

    • DOI

      10.1111/resp.13634

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reduced endogenous secretory RAGE in blood and bronchoalveolar lavage fluid is associated with poor prognosis in idiopathic pulmonary fibrosis2020

    • Author(s)
      Kakuhiro Yamaguchi, Hiroshi Iwamoto*, Witold Mazur, Shinichiro Miura, Shinjiro Sakamoto, Yasushi Horimasu, Takeshi Masuda, Shintaro Miyamoto, Taku Nakashima, Shinichiro Ohshimo, Kazunori Fujitaka, Hironobu Hamada, Noboru Hattori
    • Journal Title

      Respiratory Research

      Volume: -

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Performance Status Is a Risk Factor for Depression before the Diagnosis of Lung Cancer Patients2019

    • Author(s)
      Miwata Kei、Masuda Takeshi、Yamaguchi Kakuhiro、Sakamoto Shinjiro、Horimasu Yasushi、Miyamoto Shintaro、Nakashima Taku、Iwamoto Hiroshi、Fujitaka Kazunori、Hamada Hironobu、Hattori Noboru
    • Journal Title

      Internal Medicine

      Volume: 58 Issue: 7 Pages: 915-920

    • DOI

      10.2169/internalmedicine.1812-18

    • NAID

      130007622184

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2019-04-01
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibition of PAI‐1 limits chemotherapy resistance in lung cancer through suppressing myofibroblast characteristics of cancer‐associated fibroblasts2019

    • Author(s)
      Masuda Takeshi、Nakashima Taku、Namba Masashi、Yamaguchi Kakuhiro、Sakamoto Shinjiro、Horimasu Yasushi、Miyamoto Shintaro、Iwamoto Hiroshi、Fujitaka Kazunori、Miyata Yoshihiro、Hamada Hironobu、Okada Morihito、Hattori Noboru
    • Journal Title

      Journal of Cellular and Molecular Medicine

      Volume: 23 Issue: 4 Pages: 2984-2994

    • DOI

      10.1111/jcmm.14205

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] High preoperative C-reactive protein level is a risk factor for acute exacerbation of interstitial lung disease after non-pulmonary surgery2019

    • Author(s)
      Takao Shun、Masuda Takeshi、Yamaguchi Kakuhiro、Sakamoto Shinjiro、Horimasu Yasushi、Nakashima Taku、Miyamoto Shintaro、Iwamoto Hiroshi、Fujitaka Kazunori、Hamada Hironobu、Hattori Noboru
    • Journal Title

      Medicine

      Volume: 98 Issue: 5 Pages: e14296-e14296

    • DOI

      10.1097/md.0000000000014296

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-KL-6/MUC1 monoclonal antibody reverses resistance to trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity by capping MUC12019

    • Author(s)
      Namba Masashi、Hattori Noboru、Hamada Hironobu、Yamaguchi Kakuhiro、Okamoto Yohei、Nakashima Taku、Masuda Takeshi、Sakamoto Shinjiro、Horimasu Yasushi、Miyamoto Shintaro、Iwamoto Hiroshi、Fujitaka Kazunori、Kohno Nobuoki
    • Journal Title

      Cancer Letters

      Volume: 442 Pages: 31-39

    • DOI

      10.1016/j.canlet.2018.10.037

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Serial measurements of KL-6 for monitoring activity and recurrence of interstitial pneumonia with anti-aminoacyl-tRNA synthetase antibody2018

    • Author(s)
      Yamaguchi Kakuhiro、Iwamoto Hiroshi、Sakamoto Shinjiro、Horimasu Yasushi、Masuda Takeshi、Miyamoto Shintaro、Nakashima Taku、Ohshimo Shinichiro、Fujitaka Kazunori、Hamada Hironobu、Kohno Nobuoki、Hattori Noboru
    • Journal Title

      Medicine

      Volume: 97 Issue: 49 Pages: e13542-e13542

    • DOI

      10.1097/md.0000000000013542

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] AGER gene polymorphisms and soluble receptor for advanced glycation end product in patients with idiopathic pulmonary fibrosis.2017

    • Author(s)
      Yamaguchi K, Iwamoto H, Horimasu Y, Ohshimo S, Fujitaka K, Hamada H, Mazur W, Kohno N, Hattori N
    • Journal Title

      Respirology

      Volume: 22 Issue: 5 Pages: 965-971

    • DOI

      10.1111/resp.12995

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] AGER rs2070600 polymorphism elevates neutrophil-lymphocyte ratio and mortality in metastatic lung adenocarcinoma2017

    • Author(s)
      Yamaguchi K, Iwamoto H, Ohshimo S, et al.
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 55 Pages: 94382-94392

    • DOI

      10.18632/oncotarget.21764

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gene expression profiling of idiopathic interstitial pneumonias (IIPs): identification of potential diagnostic markers and therapeutic targets.2017

    • Author(s)
      Horimasu Y, Ishikawa N, Taniwaki M, Yamaguchi K, Hamai K, Iwamoto H, Ohshimo S, Hamada H, Hattori N, Okada M, Arihiro K, Ohtsuki Y, Kohno N
    • Journal Title

      BMC Med Genet

      Volume: 18 Issue: 1 Pages: 88-88

    • DOI

      10.1186/s12881-017-0449-9

    • NAID

      120006799363

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The extent of ground-glass attenuation is a risk factor of chemotherapy-related exacerbation of interstitial lung disease in patients with non-small cell lung cancer2017

    • Author(s)
      Masuda Takeshi, Hirano Chihiro, Horimasu Yasushi, Nakashima Taku, Miyamoto Shintarou, Iwamoto Hiroshi, Ohshimo Shinichiro, Fujitaka Kazunori, Hamada Hironobu, Hattori Noboru
    • Journal Title

      Cancer Chemotherapy and Pharmacology

      Volume: 81 Issue: 1 Pages: 131-139

    • DOI

      10.1007/s00280-017-3476-5

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] MUC1 in lung adenocarcinoma: cross-sectional genetic and serological study2017

    • Author(s)
      Horimasu Yasushi、Ishikawa Nobuhisa、Tanaka Sonosuke、Hirano Chihiro、Iwamoto Hiroshi、Ohshimo Shinichiro、Fujitaka Kazunori、Hamada Hironobu、Hattori Noboru、Kohno Nobuoki
    • Journal Title

      BMC Cancer

      Volume: 17 Issue: 1 Pages: 263-263

    • DOI

      10.1186/s12885-017-3272-y

    • NAID

      120006559419

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Serum high mobility group box 1 is associated with the onset and severity of acute exacerbation of idiopathic pulmonary fibrosis2019

    • Author(s)
      Kakuhiro Yamaguchi, Hiroshi Iwamoto, Shinjiro Sakamoto, Yasushi Horimasu, Takeshi Masuda, Shintaro Miyamoto, Taku Nakashima, Shinichiro Ohshimo, Kazunori Fujitaka, Hironobu Hamada, Noboru Hattori.
    • Organizer
      ERS international congress 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 特発性肺線維症患者における血中High mobility group box 1の検討2019

    • Author(s)
      山口覚博, 岩本博志, 坂本信二郎, 堀益 靖, 益田  武, 宮本真太郎, 中島 拓, 藤高一慶, 濱田泰伸, 服部  登.
    • Organizer
      第59回日本呼吸器学会学術講演会
    • Related Report
      2019 Annual Research Report
  • [Presentation] IPF患者における血中High mobility group box 1の検討2019

    • Author(s)
      山口 覚博、岩本 博志、坂本 信二郎、堀益 靖、益田 武、中島 拓、宮本 真太郎、藤高 一慶、濱田 泰伸、服部 登
    • Organizer
      第59回日本呼吸器学会学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] IPF患者におけるBALF中endogenous secretary RAGEの検討2019

    • Author(s)
      三浦 慎一朗、山口 覚博、坂本 信二郎、堀益 靖、益田 武、宮本 真太郎、中島 拓、岩本 博志、藤高 一慶、濱田 泰伸、服部 登
    • Organizer
      第59回日本呼吸器学会学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] IPF患者における 血中endogenous secretary RAGEの検討2018

    • Author(s)
      山口覚博, 岩本博志, 坂本信二郎, 堀益 靖, 益田  武, 宮本真太郎, 中島 拓, 藤高一慶, 濱田泰伸, 服部  登.
    • Organizer
      第 58 回日本呼吸器学会学術講演会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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