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HMGB1-induced vaspressin deficiency contributes to septic shock

Research Project

Project/Area Number 24390402
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Emergency medicine
Research InstitutionKagoshima University

Principal Investigator

ITO Takashi  鹿児島大学, 医歯(薬)学総合研究科, 講師 (20381171)

Co-Investigator(Kenkyū-buntansha) MARUYAMA Ikuro  鹿児島大学, 大学院医歯学総合研究科, 特任教授 (20082282)
Co-Investigator(Renkei-kenkyūsha) NAKAHARA Mayumi  鹿児島大学, 大学院医歯学総合研究科, 特任助教 (90707514)
KAWAHARA Ko-ichi  大阪工業大学, 工学部生命工学科, 特任教授 (10381170)
Research Collaborator NAGASATO Tomoka  藤森工業株式会社
YAMADA Shingo  株式会社シノテスト
TAKENAKA Yukari  鹿児島大学, 大学院医歯学総合研究科
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Keywords敗血症性ショック / バソプレシン / HMGB1 / DAMPs / 敗血症 / ショック / 集中治療医学 / DAMPs
Outline of Final Research Achievements

Vasopressin deficiency contributes to the vasodilatation in the later stages of septic shock, and supplementary arginine vasopressin (AVP) infusion is increasingly being used to stabilize cardiocirculatory function in patients with advanced vasodilatory shock. However, the exact mechanism responsible for the vasopressin deficiency remains to be determined. Here we show that high mobility group box 1 protein (HMGB1), a late mediator of endotoxin lethality, is responsible for the vasopressin deficiency in endotoxemic rats. Administration of a neutralizing antibody against HMGB1 increased plasma vasopressin levels in endotoxemic rats, while administration of exogenous HMGB1 decreased plasma vasopressin levels.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (16 results)

All 2015 2014 2013 2012

All Journal Article (9 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (7 results) (of which Invited: 2 results)

  • [Journal Article] Cleavage of host cytokeratin-6 by lysine-specific gingipain induces gingival inflammation in periodontitis patients.2015

    • Author(s)
      Tancharoen S, Matsuyama T, Kawahara K, Tanaka K, Lee LJ, Machigashira M, Noguchi K, Ito T, Imamura T, Potempa J, Kikuchi K,Maruyama I.
    • Journal Title

      PLoS One.

      Volume: 10 Issue: 2 Pages: e0117775-e0117775

    • DOI

      10.1371/journal.pone.0117775

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HMGB1 promotes the development of pulmonary arterial hypertension in rats.2014

    • Author(s)
      Sadamura-Takenaka Y, Ito T, Noma S, Oyama Y, Yamada S, Kawahara K, Inoue H, Maruyama I.
    • Journal Title

      PLoS One.

      Volume: 9 Issue: 7 Pages: e102482-e102482

    • DOI

      10.1371/journal.pone.0102482

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] PAMPs and DAMPs as triggers for DIC2014

    • Author(s)
      Ito T
    • Journal Title

      J Intensive Care

      Volume: 2 Issue: 1 Pages: 67-67

    • DOI

      10.1186/s40560-014-0065-0

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Roles of thrombomodulin as a nuclear safeguard2014

    • Author(s)
      伊藤隆史
    • Journal Title

      Folia Pharmacologica Japonica

      Volume: 143 Issue: 1 Pages: 18-21

    • DOI

      10.1254/fpj.143.18

    • NAID

      130004827684

    • ISSN
      0015-5691, 1347-8397
    • Related Report
      2013 Annual Research Report
  • [Journal Article] Basic research on thrombomodulin2014

    • Author(s)
      伊藤隆史
    • Journal Title

      Japanese Journal of Thrombosis and Hemostasis

      Volume: 25 Issue: 1 Pages: 55-60

    • DOI

      10.2491/jjsth.25.55

    • NAID

      130003393340

    • ISSN
      0915-7441, 1880-8808
    • Related Report
      2013 Annual Research Report
  • [Journal Article] Potential of the angiotensin receptor blockers (ARBs) telmisartan, Irbesartan, and candesartan for inhibiting the HMGB1/RAGE axis in prevention and acute treatment of stroke.2013

    • Author(s)
      Kikuchi K, Tancharoen S, Ito T, Morimoto-Yamashita Y, Miura N, Kawahara K, MaruyamaI, Murai Y, Tanaka E
    • Journal Title

      Int. Mol. Sci.

      Volume: 14 Issue: 9 Pages: 18899-18924

    • DOI

      10.3390/ijms140918899

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PAMPs/DAMPs as novel mediators of inflammation-associated thrombosis2013

    • Author(s)
      伊藤隆史
    • Journal Title

      Japanese Journal of Thrombosis and Hemostasis

      Volume: 24 Issue: 6 Pages: 675-679

    • DOI

      10.2491/jjsth.24.675

    • NAID

      130003393331

    • ISSN
      0915-7441, 1880-8808
    • Related Report
      2013 Annual Research Report
  • [Journal Article] PAMPs/DAMPs2013

    • Author(s)
      伊藤隆史
    • Journal Title

      International Review of Thrombosis

      Volume: 8 Pages: 74-76

    • Related Report
      2012 Annual Research Report
  • [Journal Article] Thrombus formation and innate immunity2012

    • Author(s)
      伊藤隆史
    • Journal Title

      Japanese Journal of Thrombosis and Hemostasis

      Volume: 23 Issue: 3 Pages: 241-246

    • DOI

      10.2491/jjsth.23.241

    • NAID

      130002077019

    • ISSN
      0915-7441, 1880-8808
    • Related Report
      2012 Annual Research Report
  • [Presentation] 敗血症性DICにおけるヒストンのnet effect2015

    • Author(s)
      伊藤隆史
    • Organizer
      第42回日本集中治療医学会学術集会
    • Place of Presentation
      東京都(ホテル日航東京)
    • Year and Date
      2015-02-10
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Extracellular histones and HMGB1in sepsis-associated coagulopathy2014

    • Author(s)
      Ito T
    • Organizer
      HMGB1 workshop in Stockholm
    • Place of Presentation
      Sweden, Stockholm(Royal Park Hotel)
    • Year and Date
      2014-09-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] DIC/TMAの新規メディエーター:ヒストン2014

    • Author(s)
      伊藤隆史
    • Organizer
      第36回日本血栓止血学会学術集会 (JSTH・救急医学会ジョイントシンポジウム)
    • Place of Presentation
      大阪府・大阪市(大阪国際交流センター)
    • Year and Date
      2014-05-30
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 生体侵襲性HMGB1-RAGEシステムと遺伝子組換えトロンボモジュリンによるインターベンション2013

    • Author(s)
      伊藤隆史
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡県 福岡市(招待講演)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 死細胞由来分子によって引き起こされる凝固異常とその制御2013

    • Author(s)
      伊藤隆史
    • Organizer
      第40回日本集中治療医学会学術集会
    • Place of Presentation
      長野県 松本市(招待講演)
    • Related Report
      2012 Annual Research Report
  • [Presentation] The Prothrombotic Roles of PAMPs and DAMPs2012

    • Author(s)
      伊藤隆史
    • Organizer
      第34回日本血栓止血学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] PAMPs/DAMPsから紐解く「敗血症の病態生理」と「トロンボモジュリンのポテンシャル」2012

    • Author(s)
      伊藤隆史
    • Organizer
      第34回日本血栓止血学会学術集会
    • Place of Presentation
      東京(招待講演)
    • Related Report
      2012 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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