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Newly development of functional low molecular therapeutics : Study of the pathomechanism of lethal multiple organ failure

Research Project

Project/Area Number 16390516
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

ABEYAMA Kazuhiro  Kagoshima University, Graduate school of Medical and Dental Sciences, Visiting associate professor, 大学院・医歯学総合研究科, 客員助教授 (30284897)

Co-Investigator(Kenkyū-buntansha) MARUYAMA Ikuro  Kagoshima University, Graduate school of Medical and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (20082282)
HASHIGUCHI Teruto  Kagoshima University, Graduate school of Medical and Dental Sciences, Associate professor, 大学院・医歯学総合研究科, 助教授 (70250917)
UCHIMURA Tomonori  Kagoshima University, University Hospital, Faculty of Medicine and Dentistry, Research Associate, 医学部・歯学部附属病院, 助手 (20363616)
鵜島 雅子  大分大学, 医学部, 助手 (90336256)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2005: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2004: ¥9,600,000 (Direct Cost: ¥9,600,000)
KeywordsHMGB1 / thrombomodulin / sepsis / DIC / lethality / anti-inflammatory peptide
Research Abstract

Extracellular HMGB1 which is released from necrotic tissue in the detrimental lesions is well known to act as "mediator of individual lethality" in the cases of sepsis and the resultant multiple organ failure (MOF). In this context, our study has revealed following evidences concerning HMGB1-related issue. 1)HMGB1 plays an important role for sustenance of inflammatory events rather than its initiation. 2)Hypoxic stress induces HMGB1 release (or secretion) in various cell types, which precedes necrotic cell death events. 3)Thrombomodulin (TM) on endothelial surface acts as an inhibitor for inflammatory activities of HMGB1. 4)The N-terminal domain (D1) of TM sequesters HMGB1 protein, which confers natural anti-inflammatory activities. For example, synthetic D1 (i.e., peptide composed of 100 amino acids) which has anti-inflammatory activities in detrimental tissue injuries, could reduce endotoxin-induced mice lethality. 5)Based on the evidences, we successfully generated a novel anti-inflammatory 12-mer peptide which contained the common sequence appears in D1 and RAGE, i.e., motif of PxxxL or LxxxP. Expectedly, the-anti-inflammatory peptide could inhibit HMGB1-RAGE signaling.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (20 results)

All 2005 2004

All Journal Article (19 results) Book (1 results)

  • [Journal Article] The N-terminal domain of thrombomodulin sequesters high-mobility group-B1 protein, a novel antiinflammatory mechanism.2005

    • Author(s)
      Abeyama K., et al.
    • Journal Title

      J Clin Invest. 115(5)

      Pages: 1267-1274

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Activated protein C, a natural anticoagulant protein, has antioxidant properties and inhibits lipid peroxidation and advanced glycation end products formation.2005

    • Author(s)
      Yamaji K., Abeyama K., et al.
    • Journal Title

      Thromb Res. 115(4)

      Pages: 319-325

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] The N-terminal domain of thrombomodulin sequesters high-mobility group-B1 protein, a novel antiinflammatory mechanism.2005

    • Author(s)
      Abeyama K, Stern DM, Ito Y, Kawahara K, Yoshimoto Y, Tanaka M, Uchimura T, Ida N, Yamazaki Y, Yamada S, Yamamoto Y, Yamamoto H, Iino S, Taniguchi N, Maruyama I.
    • Journal Title

      J Clin Invest. 115(5)

      Pages: 1267-1274

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Activated protein C, a natural anticoagulant protein, has antioxidant properties and inhibits lipid peroxidation and advanced glycation end products formation.2005

    • Author(s)
      Yamaji K, Wang Y, Liu Y, Abeyama K, Hashiguchi T, Uchimura T, Krishna Biswas K, Iwamoto H, Maruyama I.
    • Journal Title

      Thromb Res. 115(4)

      Pages: 319-325

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The N-terminal domain of thrombomodulin sequesters high-mobility group-B1 protein, a novel antiinflammatory mechanism.2005

    • Author(s)
      Abeyama K., et al.
    • Journal Title

      J Clin Invest 115(5)

      Pages: 1267-1274

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The N-Terminal Domain of Thrombomodulin Sequesters High Mobility Group-B1 Protein, a Novel Anti-inflammatory Mechanism.2005

    • Author(s)
      Abeyama K., et al.
    • Journal Title

      J Clin Invest. In press

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Activated protein C, a natural anticoagulant properties and inhibits lipid peroxidation and advanced glycation end products formation.2005

    • Author(s)
      Yamaji K., Abeyama K., et al.
    • Journal Title

      Thromb.Res. 115(4)

      Pages: 319-325

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The antimetastatic role of thrombomodulin expression in islet cell-derived tumors and its diagnostic value.2004

    • Author(s)
      Iino S., Abeyama K., et al.
    • Journal Title

      Clin Cancer Res. 10(18 pt.1)

      Pages: 6179-6188

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Decreased total nitric oxide production in patients with duchenne muscular dystrophy.2004

    • Author(s)
      Kasai T., Abeyama K., et al.
    • Journal Title

      J Biomed Sci. 11(4)

      Pages: 534-537

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Thrombomodulin expression on Langerhans' islet : can endogenous 'anticoagulant on demand' overcome detrimental thrombotic complications in clinical islet transplantation?2004

    • Author(s)
      Iino S., Abeyama K., et al.
    • Journal Title

      J Thromb Haemost. 2(5)

      Pages: 833-834

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 病態生理 : 炎症とその制御システム2004

    • Author(s)
      阿辺山和浩, 丸山征郎
    • Journal Title

      日本臨床 62(12)

      Pages: 2229-2235

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The antimetastatic role of thrombomodulin expression in islet cell-derived tumors and its diagnostic value.2004

    • Author(s)
      Iino S, Abeyama K, Kawahara K, Yamakuchi M, Hashiguchi T, Matsukita S, Yonezawa S, Taniguchi S, Nakata M, Takao S, Aikou T, Maruyama I.
    • Journal Title

      Clin Cancer Res. 10(18 pt.1)

      Pages: 6179-6188

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Decreased total nitric oxide production in patients with duchenne muscular dystrophy.2004

    • Author(s)
      Kasai T, Abeyama K, Hashiguchi T, Fukunaga H, Osame M, Maruyama I.
    • Journal Title

      J Biomed Sci. 11(4)

      Pages: 534-537

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Thrombomodulin expression on Langerhans' islet : can endogenous 'anticoagulant on demand' overcome detrimental thrombotic complications in clinical islet transplantation?2004

    • Author(s)
      Iino S, Abeyama K, Kawahara KI, Aikou T, Maruyama I.
    • Journal Title

      J Thromb Haemost. 2(5)

      Pages: 833-834

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulatory cross-talk between inflammation and blood coagulation. (in Japanese)2004

    • Author(s)
      Abeyama K, Maruyama I.
    • Journal Title

      Kekkan-Naihisaibou kenkyuu Frontier

      Pages: 21-23

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Inflammation and its regulatory system. (in Japanese)2004

    • Author(s)
      Abeyama K, Maruyama I.
    • Journal Title

      Nippon Rinsho 62(12)

      Pages: 2229-2235

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The anti-metastatic role of thrombomodulin expression in islet cell-derived tumors, and its diagnostic value.2004

    • Author(s)
      Iino S., Abeyama K., et al.
    • Journal Title

      Clin.Cancer Res. 10

      Pages: 6179-6188

    • Related Report
      2004 Annual Research Report
  • [Journal Article] (総説)病態生理 炎症とその制御システム2004

    • Author(s)
      阿辺山和浩, 丸山征郎
    • Journal Title

      日本臨床 62(12)

      Pages: 2229-2235

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 3章 血管内皮細胞による炎症・凝固系制御、-炎症反応系と血液凝固系のクロストーク-2004

    • Author(s)
      阿辺山和浩, 丸山征郎
    • Journal Title

      血管内皮細胞研究フロンティア

      Pages: 21-23

    • Related Report
      2004 Annual Research Report
  • [Book] 血管内皮細胞研究フロンティア2004

    • Author(s)
      阿辺山和浩, 丸山征郎
    • Publisher
      血管内皮細胞による炎症・凝固系制御(炎症反応系と血液凝固系のクロストーク)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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