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Clarification of the role of DAMP in health effects caused by particulate matters and risk assessment

Research Project

Project/Area Number 18H03038
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 58020:Hygiene and public health-related: including laboratory approach
Research InstitutionUniversity of Fukui

Principal Investigator

Hiraku Yusuke  福井大学, 学術研究院医学系部門, 教授 (30324510)

Co-Investigator(Kenkyū-buntansha) 田中 昭代  九州大学, 医学研究院, 講師 (10136484)
村田 真理子  三重大学, 医学系研究科, 教授 (10171141)
中野 真規子  慶應義塾大学, 医学部(信濃町), 講師 (70384906)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords粒子状物質 / 炎症 / DAMP / インジウム / リスク評価
Outline of Final Research Achievements

Particulate matters are accumulated in the respiratory systems by inhalation exposure and induce chronic inflammation, leading to carcinogenesis and fibrosis. DAMPs include molecules that are released from damaged cells to mediate inflammatory responses, such as HMGB1 and S100 family proteins. This study provided a new mechanism by which indium compounds induce DNA damage in human lung epithelial cells via the release of HMGB1 from exposed cells and inflammatory responses in neighboring cells. In lung tissues of indium-exposed rats, the expression levels of S100 family proteins were dramatically elevated. In workers with past indium exposure, serum indium and KL-6 levels remain to be high, raising concerns about the risk of lung carcinogenesis in the future. DAMP, including HMGB1 and S100 family proteins, may be used for evaluation of the risk of diseases caused by particulate matters.

Academic Significance and Societal Importance of the Research Achievements

本研究では、我々の実験研究により報告した粒子状物質による健康障害の新規分子機構に基づき、炎症反応に重要な役割を果たすDAMPに注目して、従来と全く異なる発想に基づくバイオマーカーの開発を目指す点に学術的意義および社会的意義がある。また、基礎研究および疫学研究の成果を基盤として、ヒト集団における産業化学物質による健康影響のリスク評価に発展させ、労働者の健康管理に寄与する点に創造性がある。

Report

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

    (35 results)

All 2021 2020 2019 2018 Other

All Journal Article (15 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 15 results,  Open Access: 13 results) Presentation (18 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Indium concentration in serum is an excellent predictor for assessing accumulated indium concentration in the lungs2021

    • Author(s)
      Hirata Miyuki、Nakano Makiko、Tanaka Akiyo、Omae Kazuyuki
    • Journal Title

      Journal of Occupational Health

      Volume: 63 Issue: 1 Pages: n/a

    • DOI

      10.1002/1348-9585.12207

    • NAID

      130008002883

    • ISSN
      1341-9145, 1348-9585
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nitrative DNA damage in lung epithelial cells exposed to indium nanoparticles and indium ions2020

    • Author(s)
      Ahmed S, Kobayashi H, Afroz T, Ma N, Oikawa S, Kawanishi S, Murata M, Hiraku Y
    • Journal Title

      Sci. Rep.

      Volume: 10 Issue: 1 Pages: 10741-10741

    • DOI

      10.1038/s41598-020-67488-3

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Idarubicin, an Anthracycline, Induces Oxidative DNA Damage in the Presence of Copper (II).2020

    • Author(s)
      Mizutani H, Shiga C, Imai M, Ikemura K, Kitamura Y, Ohta K, Miyazawa D, Sakanashi M, Tahira T, Maeda T, Hiraku Y, Kawanishi S.
    • Journal Title

      Anticancer Research

      Volume: 40 Issue: 10 Pages: 5399-5404

    • DOI

      10.21873/anticanres.14548

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Social and family factors as determinants of exercise habits in Japanese elementary school children: a cross-sectional study from the Super Shokuiku School Project2020

    • Author(s)
      Satomi Sawa, Michikazu Sekine, Masaaki Yamada, Yugo Fukazawa, Yusuke Hiraku
    • Journal Title

      Environmental Health and Preventive Medicine

      Volume: - Issue: 1 Pages: 54-54

    • DOI

      10.1186/s12199-020-00892-3

    • NAID

      210000158504

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combination of RERG and ZNF671 methylation rates in ccfDNA: a novel biomarker for screening of nasopharyngeal carcinoma2020

    • Author(s)
      Xu Y, Zhao W, Mo Y, Ma N, Midorikawa K, Kobayashi H, Hiraku Y, Oikawa S, Zhang Z, Huang G, Takeuchi K, Murata M.
    • Journal Title

      Cancer Sci.

      Volume: Epub ahead of prin Issue: 7 Pages: 2536-2545

    • DOI

      10.1111/cas.14431

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Possibility of lung cancer risk in indium-exposed workers: An 11-year multicenter cohort study2019

    • Author(s)
      Nakano M, Omae K, Tanaka A, Hirata M.
    • Journal Title

      Journal of Occupational Health

      Volume: 61 Issue: 3 Pages: 251-256

    • DOI

      10.1002/1348-9585.12050

    • NAID

      130007653230

    • ISSN
      1341-9145, 1348-9585
    • Year and Date
      2019-05-20
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pathway linking physical activity, sleep duration, and breakfast consumption with the physical/psychosocial health of schoolchildren2019

    • Author(s)
      Sawa S, Hashizume K, Abe T, Kusaka Y, Fukazawa Y, Hiraku Y, Hagihara A
    • Journal Title

      J Child Health Care

      Volume: - Issue: 1 Pages: 5-17

    • DOI

      10.1177/1367493519891019

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-Cancer Mechanisms of Taurine in Human Nasopharyngeal Carcinoma Cells2019

    • Author(s)
      He Feng、Ma Ning、Midorikawa Kaoru、Hiraku Yusuke、Oikawa Shinji、Mo Yingxi、Zhang Zhe、Takeuchi Kazuhiko、Murata Mariko
    • Journal Title

      Adv Exp Med Biol

      Volume: 2019;1155:533-541 Pages: 533-541

    • DOI

      10.1007/978-981-13-8023-5_49

    • ISBN
      9789811380228, 9789811380235
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oxidative DNA damage and apoptosis induced by aclarubicin, an anthracycline: role of hydrogen peroxide and copper.2019

    • Author(s)
      Mizutani H, Hayashi Y, Hashimoto M, Imai M, Ichimaru Y, Kitamura Y, Ikemura K, Miyazawa D, Ohta K, Ikeda Y, Maeda T, Yoshikawa M, Hiraku Y, Kawanishi S
    • Journal Title

      Anticancer Res

      Volume: 39 Issue: 7 Pages: 3443-3451

    • DOI

      10.21873/anticanres.13490

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mechanisms of DNA damage induced by morin, an inhibitor of amyloid β-peptide aggregation2019

    • Author(s)
      Mori Yurie、Kato Shinya、Fujisawa Yutaka、Ohnishi Shiho、Hiraku Yusuke、Kawanishi Shosuke、Murata Mariko、Oikawa Shinji
    • Journal Title

      Free Radical Research

      Volume: 53 Issue: 1 Pages: 115-123

    • DOI

      10.1080/10715762.2018.1562179

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of CD44 Variant 9: A Novel Cancer Stem Cell Marker in Human Cholangiocarcinoma in Relation to Inflammation2018

    • Author(s)
      Suwannakul Nattawan、Ma Ning、Thanan Raynoo、Pinlaor Somchai、Ungarreevittaya Piti、Midorikawa Kaoru、Hiraku Yusuke、Oikawa Shinji、Kawanishi Shosuke、Murata Mariko
    • Journal Title

      Mediators of Inflammation

      Volume: 2018 Pages: 1-8

    • DOI

      10.1155/2018/4867234

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oxidative DNA damage induced by pirarubicin, an anthracycline anticancer agent, in the presence of copper(II).2018

    • Author(s)
      Mizutani H, Nishimoto A, Hotta S, Ikemura K, Imai M, Miyazawa D, Ohta K, Ikeda Y, Maeda T, Yoshikawa M, Hiraku Y, Kawanishi S
    • Journal Title

      Anticancer Research

      Volume: 38 Issue: 5 Pages: 2643-2648

    • DOI

      10.21873/anticanres.12506

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Proteomic profiling of exosomal proteins for blood-based biomarkers in Parkinson's Disease.2018

    • Author(s)
      Kitamura Y, Kojima M, Kurosawa T, Sasaki R, Ichihara S, Hiraku Y, Tomimoto H, Murata M, Oikawa S.
    • Journal Title

      Neuroscience

      Volume: 392 Pages: 121-128

    • DOI

      10.1016/j.neuroscience.2018.09.017

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Taurine exhibits an apoptosis-inducing effect on human nasopharyngeal carcinoma cells through PTEN/Akt pathways in vitro2018

    • Author(s)
      He Feng、Ma Ning、Midorikawa Kaoru、Hiraku Yusuke、Oikawa Shinji、Zhang Zhe、Huang Guangwu、Takeuchi Kazuhiko、Murata Mariko
    • Journal Title

      Amino Acids

      Volume: 50 Issue: 12 Pages: 1749-1758

    • DOI

      10.1007/s00726-018-2651-2

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Environmental Factors and MicroRNA: Application for DOHaD Research and Future Perspectives2018

    • Author(s)
      平工雄介
    • Journal Title

      Nippon Eiseigaku Zasshi (Japanese Journal of Hygiene)

      Volume: 73 Issue: 2 Pages: 105-109

    • DOI

      10.1265/jjh.73.105

    • NAID

      130007378538

    • ISSN
      0021-5082, 1882-6482
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] SIRT3/SOD2の阻害を介したメラトニンによるシコニン誘発癌細胞死の増強2021

    • Author(s)
      Mengling Li, Qianwen Feng, Yulin Li, Shahbaz Ahmad Zakki, Yusuke Hiraku, Zheng-Guo Cui, Hidekuni Inadera
    • Organizer
      第91回日本衛生学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Melatonin sensitizes phenylarsine oxide via induction of apoptosis and results in strong anticancer potential2021

    • Author(s)
      Zheng-Guo Cui, Shahbaz Ahmad Zakki, Mengling Li, Qianwen Feng, Yulin Li, Yusuke Hiraku, Hidekuni Inadera
    • Organizer
      第91回日本衛生学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Study on the application of ILO International Classification of Radiographs of Pneumoconioses among physicians from Asian countries2020

    • Author(s)
      Naw Awm JP, Taro Tamura, Yukinori Kusaka, Yusuke Hiraku, Narufumi Suganuma
    • Organizer
      第93回日本産業衛生学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ベトナム炭鉱労働者のじん肺についての一年間の追跡調査2020

    • Author(s)
      宇野友康、田村太朗、日下幸則、金山ひとみ、平工雄介
    • Organizer
      第93回日本産業衛生学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] インジウム化合物に曝露した肺上皮細胞における炎症反応を介したニトロ化DNA損傷2020

    • Author(s)
      Sharif Ahmed、小林果、Tahmina Afroz、馬寧、及川伸二、川西正祐、 村田真理子、平工雄介
    • Organizer
      第90回日本衛生学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] インジウム化合物によるヒト肺上皮細胞におけるニトロ化DNA損傷2019

    • Author(s)
      平工雄介、村田真理子
    • Organizer
      第92回日本産業衛生学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 環境因子によるマイクロRNAの発現変動:DOHaD研究への応用と展望2019

    • Author(s)
      平工雄介
    • Organizer
      第13回DOHaD疫学セミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 環境発がんにおける酸化・ニトロ化DNA損傷2019

    • Author(s)
      平工雄介
    • Organizer
      第51回藤田学園医学会シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] (若手自由集会、日本医学会連合加盟学会連携フォーラム) タイ肝吸虫感染による胆管癌の予防を目指した国際共同研究2019

    • Author(s)
      平工雄介
    • Organizer
      第89回日本衛生学会学術総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Nitrative DNA damage in lung epithelial cells exposed to particulate and soluble indium compounds (肺上皮細胞における粒子状および水溶性インジウム化合物によるニトロ化DNA損傷)2019

    • Author(s)
      Sharif Ahmed, Tahmina Afroz, 馬寧、川西正祐、村田真理子、平工雄介
    • Organizer
      第89回日本衛生学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] RERG hypermethylation in circulating cell-free DNA of nasopharyngeal carcinoma: a potential hematological marker for screening2019

    • Author(s)
      Yifei Xu, Ning Ma, Kaoru Midorikawa, Yusuke Hiraku, Shinji Oikawa, Mariko Murata
    • Organizer
      第89回日本衛生学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Taurine exhibits an anti-proliferation effect on human nasopharyngeal carcinoma cells in vivo2019

    • Author(s)
      Feng He, Ning Ma, Kaoru Midorikawa, Yusuke Hiraku, Shinji Oikawa, Kazuhiko Takeuchi, Mariko Murata
    • Organizer
      第89回日本衛生学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 抗がん性抗生物質アクラルビシンによる酸化的DNA損傷と細胞死2019

    • Author(s)
      水谷秀樹、橋本未耶美、平工雄介、川西正祐
    • Organizer
      日本酸化ストレス学会東海支部第7回学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] GDF10 is a candidate tumor suppressor gene inactivated by promoter hypermethylation in human nasopharyngeal carcinoma2018

    • Author(s)
      Feng He, Ning Ma, Kaoru Midorikawa, Yusuke Hiraku, Shinji Oikawa, Zhe Zhang, Guangwu Huang, Kazuhiko Takeuchi, Mariko Murata
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] A novel cancer stem cell biomarker CD44v9 in liver fluke-related cholangiocarcinoma2018

    • Author(s)
      Nattawan Suwannakul, Ning Ma, Raynoo Thanan, Somchai Pinlaor, Kaoru Midorikawa, Yusuke Hiraku, Shinji Oikawa, Shosuke Kawanishi, Mariko Murata.
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] DNA methylation in circulating cell-free DNA of nasopharyngeal carcinoma2018

    • Author(s)
      Yifei Xu, Ning Ma, Kaoru Midorikawa, Yusuke Hiraku, Shinji Oikawa, Zhe Zhang, Guangwu Huang, Kazuhiko Takeuchi, Mariko Murata
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 石綿曝露マウスの肺組織におけるマイクロRNAと標的遺伝子発現の解析2018

    • Author(s)
      平工雄介、村田真理子
    • Organizer
      第91回日本産業衛生学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Taurine induces Apoptosis in Human Nasopharyngeal Carcinoma Cells through PTEN-mediated inhibition of Akt pathway in Vitro.2018

    • Author(s)
      Feng He, Ning Ma, Kaoru Midorikawa, Yusuke Hiraku, Shinji Oikawa, Kazuhiko Takeuchi, Mariko Murata
    • Organizer
      The 21st International Taurine Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Book] 図解 腫瘍薬学(川西正祐、賀川義之、大井一弥 編)2020

    • Author(s)
      平工雄介、川西正祐
    • Total Pages
      677
    • Publisher
      南山堂
    • ISBN
      9784525721619
    • Related Report
      2020 Annual Research Report
  • [Remarks] 福井大学医学部 環境保健学分野

    • URL

      https://www.med.u-fukui.ac.jp/laboratory/environmental/

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report 2018 Annual Research Report

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

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