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Novel therapeutic proposal for DIC/Shock: from Damage-Sensing/-Control to Damage Resolution

Research Project

Project/Area Number 17H04363
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Emergency medicine
Research InstitutionKagoshima University

Principal Investigator

MARUYAMA Ikuro  鹿児島大学, 医歯学総合研究科, 特任教授 (20082282)

Co-Investigator(Kenkyū-buntansha) 垣花 泰之  鹿児島大学, 医歯学域医学系, 教授 (20264426)
川原 幸一  大阪工業大学, 工学部, 教授 (10381170)
山口 宗一  鹿児島大学, 医歯学域医学系, 准教授 (20325814)
原田 陽一郎  地方独立行政法人大阪府立病院機構大阪国際がんセンター(研究所), その他部局等, 糖鎖オンコロジー部主任研究員 (80464147)
伊藤 隆史  鹿児島大学, 医歯学総合研究科, 講師 (20381171)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2019: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2018: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2017: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
KeywordsHMGB1 / DAMPs / PAMPs / RAMPs / 生体損傷 / DIC / トロンボモジュリン / プロテインC / 組織損傷 / 止血 / 修復 / Thrombin / Thrombomodulin / TM / Protein C / EPCR / DAMPs / RAMPs / thrombin / protein C / PAMPs
Outline of Final Research Achievements

A typical DAMP, HMGB1 has 3-SH groups in its. Therefore, it has 3 types of isoforms based on their redox states, all reduced, partial oxidative and all oxidation type, with different activities. The all reduced type shows the chemoattractant for inflammatory cells, and partially oxidative one activates the inflammatory cells resulting the secretion of inflammatory cytokines. However, all oxidative one expresses the anti-inflammatory activities at the local injury sites. Therefore, it is crucial to evaluate HMGB1 not only by quantitatively but also qualitatively. We have been trying to establish the method to evaluate these isoforms individually. At the first we tried to establish the specific monoclonal antibodies which react specifically react 3 isoforms individually. At present we succeeded in the establishment of the monoclonal antibody which highly specifically react to all reduced HMGB1. Using this, we have started to establish the all reduced type HMGB1 assay kit.

Academic Significance and Societal Importance of the Research Achievements

DAMP:HMGB1が生体損傷の運命を決めることに関して、筆者らは世界の本領既の研究をリードしてきた。即ち、測定法の開発を開発し、生体損傷のマーカーであることを検証、発表してきた。しかしHMGB1には3つのアイソフォームが存在し、全酸化型は修復に働くことが判明してきた。そのためHMGB1の質的測定が重要であり、本研究は、生体保護・修復活性のある本分子の測定法の端緒をつかみつつあるという意義深い研究である。

Report

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

    (18 results)

All 2020 2019 2018 2017

All Journal Article (11 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 11 results,  Open Access: 10 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 7 results)

  • [Journal Article] Leukocyte-derived extracellular DNA contributes to abnormal pressure elevation in the extracorporeal circulation circuit2020

    • Author(s)
      Yashima Nozomi、Ito Takashi、Kajiyama Kenji、Maeda Hiroyuki、Kakihana Yasuyuki、Maruyama Ikuro
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1

    • DOI

      10.1038/s41598-019-57173-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum histone H3 levels and platelet counts are potential markers for coagulopathy with high risk of death in septic patients: a single-center observational study2019

    • Author(s)
      Ito Takashi、Totoki Takaaki、Yokoyama Yayoi、Yasuda Tomotsugu、Furubeppu Hiroaki、Yamada Shingo、Maruyama Ikuro、Kakihana Yasuyuki
    • Journal Title

      Journal of Intensive Care

      Volume: 7 Issue: 1 Pages: 63-63

    • DOI

      10.1186/s40560-019-0420-2

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recombinant Thrombomodulin Suppresses Histone-Induced Neutrophil Extracellular Trap Formation2019

    • Author(s)
      Shrestha Binita、Ito Takashi、Kakuuchi Midori、Totoki Takaaki、Nagasato Tomoka、Yamamoto Mika、Maruyama Ikuro
    • Journal Title

      Frontiers in Immunology

      Volume: 10 Pages: 2535-2535

    • DOI

      10.3389/fimmu.2019.02535

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Application of high-mannose-type glycan-specific lectin from Oscillatoria Agardhii for affinity isolation of tumor-derived extracellular vesicles2019

    • Author(s)
      Yamamoto Mika、Harada Yoichiro、Suzuki Takehiro、Fukushige Tomoko、Yamakuchi Munekazu、Kanekura Takuro、Dohmae Naoshi、Hori Kanji、Maruyama Ikuro
    • Journal Title

      Analytical Biochemistry

      Volume: 580 Pages: 21-29

    • DOI

      10.1016/j.ab.2019.06.001

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dynamics of Soluble Thrombomodulin and Circulating miRNAs in Patients with Atrial Fibrillation Undergoing Radiofrequency Catheter Ablation2019

    • Author(s)
      Namino F, Yamakuchi M, Iriki Y, Okui H, Ichiki H, Maenosono R, Oketani N, Masamoto I, Miyata M, Horiuchi M, Hashiguchi T, Ohishi M, Maruyama I
    • Journal Title

      Clin Appl Thromb Hemost

      Volume: 25 Pages: 107602961985157-107602961985157

    • DOI

      10.1177/1076029619851570

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Circulating histone H3 levels in septic patients are associated with coagulopathy, multiple organ failure, and death: a single-center observational study2019

    • Author(s)
      Yokoyama Yayoi、Ito Takashi、Yasuda Tomotsugu、Furubeppu Hiroaki、Kamikokuryo Chinatsu、Yamada Shingo、Maruyama Ikuro、Kakihana Yasuyuki
    • Journal Title

      Thrombosis Journal

      Volume: 17 Issue: 1 Pages: 1-1

    • DOI

      10.1186/s12959-018-0190-4

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison between blood coagulability in the intra-atrial and peripheral regions during the acute phase after rapid atrial pacing2019

    • Author(s)
      Yamada S, Hirao D, Miura N, Iwanaga T, Kawaguchi T, Yoshimura A, Oomori T, Nagasato T, Maruyama I, Fukushima R
    • Journal Title

      Experimental Animals

      Volume: 68 Issue: 2 Pages: 137-146

    • DOI

      10.1538/expanim.18-0100

    • NAID

      130007642989

    • ISSN
      0007-5124, 1341-1357, 1881-7122
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Circulating histone H3 levels are increased in septic mice in a neutrophil-dependent manner: preclinical evaluation of a novel sandwich ELISA for histone H32018

    • Author(s)
      Ito Takashi、Nakahara Mayumi、Masuda Yoshiki、Ono Sachie、Yamada Shingo、Ishikura Hiroyasu、Imaizumi Hitoshi、Kamikokuryo Chinatsu、Kakihana Yasuyuki、Maruyama Ikuro
    • Journal Title

      Journal of Intensive Care

      Volume: 6 Issue: 1 Pages: 79-79

    • DOI

      10.1186/s40560-018-0348-y

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Circulating activated protein C levels are not increased in septic patients treated with recombinant human soluble thrombomodulin2018

    • Author(s)
      Arishima Takuro、Ito Takashi、Yasuda Tomotsugu、Yashima Nozomi、Furubeppu Hiroaki、Kamikokuryo Chinatsu、Futatsuki Takahiro、Madokoro Yutaro、Miyamoto Shotaro、Eguchi Tomohiro、Haraura Hiroyuki、Maruyama Ikuro、Kakihana Yasuyuki
    • Journal Title

      Thrombosis Journal

      Volume: 16 Issue: 1 Pages: 24-24

    • DOI

      10.1186/s12959-018-0178-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HMGB proteins and arthritis.2018

    • Author(s)
      Taniguchi N, Kawakami Y, Maruyama I, Lotz M.
    • Journal Title

      Hum Cell

      Volume: 31(1) Issue: 1 Pages: 1-9

    • DOI

      10.1007/s13577-017-0182-x

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Decreased Expression of Thrombomodulin in Endothelial Cells by Fibroblast Growth Factor-23/α-Klotho.2017

    • Author(s)
      Tanaka K, Salunya T, Motomiya Y, Motomiya Y, Oyama Y, Yamakuchi M, Maruyama I.
    • Journal Title

      Ther Apher Dial

      Volume: 21(4) Issue: 4 Pages: 395-404

    • DOI

      10.1111/1744-9987.12524

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] recombinant TM の開発ーDICトリガー因子:トロンビンのベクトル変換によるDIC治療ストラテジー2019

    • Author(s)
      丸山 征郎
    • Organizer
      第41回日本血栓止血学会学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Endothelial anticoagulant thrombomodulin binds and neutralizes HMGB1, histones and LPS, and induces resolution of damage through protein C activation2019

    • Author(s)
      Ikuro Maruyama
    • Organizer
      9th International DAMPs and Alarmins Symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 急性血液浄化の新視点:exosomeとRAMPs2018

    • Author(s)
      丸山 征郎
    • Organizer
      第29回日本急性血液浄化学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 病態拡大の新しい使者:exosomeが参画した新しいショック病2018

    • Author(s)
      丸山 征郎
    • Organizer
      第33回日本Shock学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 血管作動因子としてのPAMPs/DAMPsとその作用2018

    • Author(s)
      丸山征郎
    • Organizer
      第47回日本心脈管作動物質学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] エクソソームとshock、炎症との関わり2017

    • Author(s)
      丸山征郎
    • Organizer
      日本集中治療医学会 第1回東海北陸支部学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 血管内皮細胞と動脈硬化2017

    • Author(s)
      丸山征郎
    • Organizer
      第49回日本動脈硬化学会総会・学術集会
    • Related Report
      2017 Annual Research Report
    • Invited

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

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