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Search for extracellular vesicles that contribute to the reduction of radiation-induced tissue damage and application to radiation emergency medicine

Research Project

Project/Area Number 18K18190
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 63020:Radiation influence-related
Research InstitutionHirosaki University

Principal Investigator

Yamaguchi Masaru  弘前大学, 保健学研究科, 助教 (00782822)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords放射線被ばく / 急性放射線症候群 / 放射線緩和剤 / 放射線防護剤 / 細胞外小胞 / TPO受容体作動薬 / 致死線量放射線 / 個体救命 / 放射線障害緩和 / 国内承認薬 / 緊急被ばく医療 / 放射線影響緩和 / マウスモデル / 放射線緩和
Outline of Final Research Achievements

Survival of lethal dose radiation-exposed mice was confirmed by administration of TPO receptor agonists, and megakaryocyte hematopoiesis was observed in the spleen and lungs of surviving individuals. These are thought to be involved in the suppression of thrombocytopenia induced in acute radiation syndrome. In microarray analysis and PCR analysis using circulating RNA, the expression of miR-296-5p, miR-486-5p, and miR-328-3p associated with leukemia development was significantly suppressed by drug administration. It was suggested that it may be a miRNA that shows the damage induced by acute radiation syndrome and/or drug-induced mitigative information. Furthermore, it was suggested that serum exosomes in surviving individuals may have a life-saving effect on individuals exposed to lethal doses of radiation.

Academic Significance and Societal Importance of the Research Achievements

福島第一原発事故に伴う廃炉作業や除染作業に伴う被ばくリスク、更に核関連施設での事故や今後の核テロの脅威に対しても早急に対策を講じる必要がある。細胞外小胞には、由来する細胞の種類に依存した多様な種類の分子が含まれ、放射線損傷又は障害軽減応答に特異的な分子が内在している可能性があり、生体内分子を緊急被ばく医療対策に応用することを視野に入れた新たなアプローチとなる。さらに、放射線による組織障害を治癒再生する可能性が期待され、がん放射線治療に伴う副作用軽減の開発に向けた示唆が得られる。また、これまでに医療被ばくががん発症率向上に寄与するという報告もあり、医療被ばく対策の一助にもなり得る。

Report

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

    (27 results)

All 2021 2020 2019 2018

All Journal Article (14 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 14 results,  Open Access: 11 results) Presentation (13 results) (of which Int'l Joint Research: 11 results,  Invited: 4 results)

  • [Journal Article] A unique high natural background radiation area ? Dose assessment and perspectives2021

    • Author(s)
      M. Hosoda, E. D. Nugraha, N. Akata, R. Yamada, Y. Tamakuma, M. Sasaki, K. Kelleher, S. Yoshinaga, T. Suzuki, C. Pornnumpa, M. Furukawa, M. Yamaguchi, K. Iwaoka, T. Sanada, T. Miura, Kusdiana, D. Iskandar, E. Pudjadi, I. Kashiwakura, S. Tokonami
    • Journal Title

      Science of The Total Environment

      Volume: 750 Pages: 142346-142346

    • DOI

      10.1016/j.scitotenv.2020.142346

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Discriminative Measurement of Absorbed Dose Rates in Air from Natural and Artificial Radionuclides in Namie Town, Fukushima Prefecture2021

    • Author(s)
      Ogura Koya, Hosoda Masahiro, Tamakuma Yuki, Suzuki Takahito, Yamada Ryohei, Negami Ryoju, Tsujiguchi Takakiyo, Yamaguchi Masaru, Shiroma Yoshitaka, Iwaoka Kazuki, Akata Naofumi, Shimizu Mayumi, Kashiwakura Ikuo, Tokonami Shinji
    • Journal Title

      International Journal of Environmental Research and Public Health

      Volume: 18 Issue: 3 Pages: 978-978

    • DOI

      10.3390/ijerph18030978

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of Antioxidant Stress-Responsive Transcription Factor Nrf2 Target Gene in the Reduction of Radiation Damage by the Thrombocytopenia Drug Romiplostim2020

    • Author(s)
      Chiba Akane、Kawabata Nanami、Yamaguchi Masaru、Tokonami Shinji、Kashiwakura Ikuo
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 43 Issue: 12 Pages: 1876-1883

    • DOI

      10.1248/bpb.b20-00442

    • NAID

      130007948724

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2020-12-01
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mitigative efficacy of the clinical dosage administration of granulocyte colony-stimulating factor and romiplostim in mice with severe acute radiation syndrome2020

    • Author(s)
      Yamaguchi Masaru、Suzuki Marino、Funaba Moeri、Chiba Akane、Kashiwakura Ikuo
    • Journal Title

      Stem Cell Research & Therapy

      Volume: 11 Issue: 1 Pages: 339-339

    • DOI

      10.1186/s13287-020-01861-x

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Proteomic changes by radio-mitigative thrombopoietin receptor agonist romiplostim in the blood of mice exposed to lethal total-body irradiation2020

    • Author(s)
      Nishida T, Yamaguchi M, Tatara Y, Kashiwakura I
    • Journal Title

      International journal of radiation biology

      Volume: 96 Issue: 9 Pages: 1125-1134

    • DOI

      10.1080/09553002.2020.1787546

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of Radiation-Dose-Dependent Expressive Genes in Individuals Exposed to External Ionizing Radiation.2020

    • Author(s)
      Yamaguchi M, Nishida T, Sato Y, Nakai Y, Kashiwakura I.
    • Journal Title

      Radiat Res.

      Volume: 193 Issue: 3 Pages: 274-285

    • DOI

      10.1667/rr15532.1

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Radiomitigative Effects of Approved Hematopoietic Drugs on Mice Exposed to Lethal Total-body Irradiation2020

    • Author(s)
      Teruki Nishida, Masaru Yamaguchi, Mukh Syaifudin, Ikuo Kashiwakura
    • Journal Title

      Atom Indonesia

      Volume: -

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] THE RELATIONSHIP BETWEEN THE MITIGATIVE EFFECTS OF ROMIPLOSTIM ON THE SURVIVAL OF MICE EXPOSED TO LETHAL IONIZING RADIATION AND THE SERUM MIRNA EXPRESSIONS2020

    • Author(s)
      Yamaguchi M, Tujiguchi T, Kashiwakura I
    • Journal Title

      Radiation Protection Dosimetry

      Volume: -

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] IKKβ Inhibitor IMD-0354 Attenuates Radiation Damage in Whole-body X-Irradiated Mice.2019

    • Author(s)
      Waga K, Yamaguchi M, Miura S, Nishida T, Itai A, Nakanishi R, Kashiwakura I.
    • Journal Title

      Oxid Med Cell Longev.

      Volume: - Pages: 1-9

    • DOI

      10.1155/2019/5340290

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diverse functions of the thrombopoietin receptor agonist romiplostim rescue individuals exposed to lethal radiation.2019

    • Author(s)
      Yamaguchi M, Hirouchi T, Yoshioka H, Watanabe J, Kashiwakura I
    • Journal Title

      Free Radic Biol Med

      Volume: 136 Pages: 60-75

    • DOI

      10.1016/j.freeradbiomed.2019.03.023

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dose-Dependent Increase of Nrf2 Target Gene Expression in Mice Exposed to Ionizing Radiation2019

    • Author(s)
      Miura Shuta、Yamaguchi Masaru、Yoshino Hironori、Nakai Yuji、Kashiwakura Ikuo
    • Journal Title

      Radiation Research

      Volume: 191 Issue: 2 Pages: 176-188

    • DOI

      10.1667/rr15203.1

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparative Study of Performance using Five Different Gamma-ray Spectrometers for Thyroid Monitoring under Nuclear Emergency Situations.2019

    • Author(s)
      Hosoda M, Iwaoka K, Tokonami S, Tamakuma Y, Shiroma Y, Fukuhara T, Imajyo Y, Taniguchi J, Akata N, Osanai M, Tsujiguchi T, Yamaguchi M, Kashiwakura I
    • Journal Title

      Health Phys

      Volume: 116 Issue: 1 Pages: 81-87

    • DOI

      10.1097/hp.0000000000000954

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The thrombopoietin mimetic romiplostim leads to the complete rescue of mice exposed to lethal ionizing radiation.2018

    • Author(s)
      Yamaguchi M, Hirouchi T, Yokoyama K, Nishiyama A, Murakami S, Kashiwakura I
    • Journal Title

      Sci Rep

      Volume: 8 Issue: 1 Pages: 10659-10659

    • DOI

      10.1038/s41598-018-29013-5

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protective Effect of the c-mpl Agonist Romiplostim on Megakaryocytopoiesis of Human CD34+ Hematopoietic Progenitor Cells Exposed to Ionizing Radiation.2018

    • Author(s)
      Monzen S, Kimura S, Yamaguchi M, Kashiwakura I
    • Journal Title

      J Interferon Cytokine Res

      Volume: 38 Issue: 5 Pages: 206-212

    • DOI

      10.1089/jir.2017.0104

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Research activities related to the radiation biodosimetry and reduction of radiation-induced disorders2020

    • Author(s)
      M. Yamaguchi, I. Kashiwakura
    • Organizer
      2020 KIRAMS - Hirosaki University Webinar on Radiation Emergency Medicine
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of e-learning materials of the trauma treatment for the patients with radioactive contamination2020

    • Author(s)
      T. Koiwa, M. Narita, M. Sakamoto, Y. Suzuki, K. Narumi, K. Yamanouchi, M. Yamaguchi, T. Tsujiguchi, K. Ito, E. Tsuruga
    • Organizer
      The 3rd Workshop on Radiation Research and Its Related Issue 2020 & The 7th Educational Symposium on RADIATION and HEALTH by young scientists (ESRAH2020)
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Regulation of antioxidant stress-responsive transcription factor Nrf2 target gene in the reduction of radiation damage by the thrombocytopenia drug Romiplostim2020

    • Author(s)
      A Chiba, M yamaguchi, I Kashiwakura
    • Organizer
      The 3rd Workshop on Radiation Research and Its Related Issue 2020 & The 7th Educational Symposium on RADIATION and HEALTH by young scientists (ESRAH2020)
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Diverse functions of the thrombopoietin receptor agonist romiplostim rescue individuals exposed to lethal radiation2019

    • Author(s)
      Yamaguchi M, Kashiwakura I
    • Organizer
      2019 3rd KIRAMS-Hirosaki University Joint Symposium Programs
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Identification of the radiation dose-responsive gene expression in mice exposed to total-body irradiation2019

    • Author(s)
      Nishida T, Yamaguchi M, et al
    • Organizer
      6th Educational symposium on radiation adn health by young scientists
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Romiplostim regulates the activation of master redox regulator Keap1-Nrf2 system in mice exposed to lethal total-body irradiation2019

    • Author(s)
      Chiba A, Yamaguchi M, et al
    • Organizer
      6th Educational symposium on radiation adn health by young scientists
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Functional characteristics of radiation response genes in human CD34+ hematopoietic stem/progenitor cells2019

    • Author(s)
      Ishikawa J, Yamaguchi M, et al
    • Organizer
      16th International Congress of Radiation Research(ICRR2019)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Diverse functions of the thrombopoietin receptor agonist romiplostim rescue individuals exposed to lethal radiation2019

    • Author(s)
      Yamaguchi M, Kashiwakura I
    • Organizer
      16th International Congress of Radiation Research(ICRR2019)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Radio-mitigative effect of domestically approved pharmaceutical drug Romiplostim on mice2019

    • Author(s)
      Masaru Yamaguchi, Ikuo Kashiwakura
    • Organizer
      “Expert Mission on Mamuju Projects” Joint Research (MoU) BATAN & Hirosaki University
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 高線量放射線被ばく個体に対する国内承認薬ロミプロスチムの放射線緩和効果2019

    • Author(s)
      山口平、柏倉幾郎
    • Organizer
      第24回日本災害医学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Diverse functions of the thrombopoietin receptor agonist romiplostim rescue individuals exposed to lethal radiation2018

    • Author(s)
      Masaru Yamaguchi, Ikuo kashiwakura
    • Organizer
      Workshop on Radiation Research and its Related Issues
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 高線量放射線被ばく個体に対する国内承認薬ロミプロスチムの放射線緩和効果2018

    • Author(s)
      山口平、廣内篤久、柏倉幾郎
    • Organizer
      日本放射線影響学会第61回大会
    • Related Report
      2018 Research-status Report
  • [Presentation] The relationship between the mitigative effects of romiplostim on the survival of mice exposed to lethal ionizing radiation and the serum miRNA expression2018

    • Author(s)
      Masaru Yamaguchi, Ikuo Kashiwakura
    • Organizer
      9th International Conference on High Level Environmental Radiation Areas - For Understanding Chronic Low-Dose-Rate Radiation Exposure Health Effects and Social Impacts
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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

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