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Thrombomodulin : As a regulator of multiple mediators

Research Project

Project/Area Number 17390282
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionKagoshima University

Principal Investigator

MARUYAMA Ikuro  Kagoshima University, Graduate School of Medical and Dental Sciences, Professor (20082282)

Co-Investigator(Kenkyū-buntansha) ABEYAMA Kazuhiro  Kagoshima University, Graduate School of Medical and Dental Sciences, Research Associate Professor (30284897)
HASHIGUCHI Teruto  Kagoshima University, Graduate School of Medical and Dental Sciences, Associate Professor (70250917)
UCHIMURA Tomonori  Kagoshima University, Medical and Dental Hospital, Assistant Professor (20363616)
ITO Takashi  Kagoshima University, Medical and Dental Hospital, Clinical Fellow (20381171)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥16,140,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2007: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2006: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2005: ¥5,500,000 (Direct Cost: ¥5,500,000)
Keywordshrombomodulin / thromb in / DIC / ock / sprvqis / radical / HMGB1 / 播種性血管内凝固症候群(DIC) / 救命 / 循環器・高血圧 / 免疫学
Research Abstract

Thrombomodulin : as a multimediator modulator
Thrombomodulin ? is a membrane protein which convert thrombin from a procoagulant protease to an anticoagulant.
This anticoagulant effect of TM is accomplished by 4th, 5th and 6th EGF-like structure. We previously showed that TM also has a radical scavenging activity.
HMGB1, a DNA binding nuclear protein, plays a crucial role for maintenance of DNA architecture and transcription. However the protein also exerts physiological and pathological roles in extracellular space through receptors including receptor for advanced glycation endprducts (RAGE) and toll like receptors-2, and -4.
We identified here that HMGB1 acts as an inducing factor for wound healing through not only mobilization and proliferation of progenitor cells, but also activation of monocytes/macrophages and dendritc cells. The activation of these monocytic lineage cells results tissue factor expression and induction of innate immunity. These may have a crucial role for hemostasis a … More nd prevention of infections in injurious sites. Thus localized HMGB1 released from necrotic cells and activated monocytes/ macrophages acts as a pleiotropic mediator in immunity and hemostasis leading wound repair.
However it has been identified that systemic, circulating HMGB 1 acts as a mediator of multiple organ failure and septic shock. We also showed that HMGB1 induces acute lung injury, hypotensive shock and disseminated intravasucular coasulation (DIC) both in humans and exoerimental animals. Based on these descriptions and observations, we intended to explore the intervention strategy for circulating HMGB1. Since we previously discovered that N-terminus of thrombomodulin binds HMGB 1 and neutralizes its proinflammatory action, we evaluated the effect of thromboodulin in experimental septic shock model. Recombinant thrombomodulin efficiently improved the DIC status and organ damage. This effect might be accomplished by scavenging effects not only thrombin but also HMGB1. These preliminary data show that TM might be beneficial for the treatment ofDIC, SIRS andendotoxin shock through scavenging multiple mediators including thrombin and HMGB1. Less

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (21 results)

All 2007 2006 2005

All Journal Article (21 results) (of which Peer Reviewed: 9 results)

  • [Journal Article] High-mobility group box 1 protein promotes development of microvascular thrombosis in rats2007

    • Author(s)
      Ito T, Maruyama I, et. al.
    • Journal Title

      J Thromb Haemost 5(1)

      Pages: 109-16

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] High-mobility group box ; protein promotes development of microvascula thrombosis in rats2007

    • Author(s)
      Ito, T., Maruyama, I., et. al.
    • Journal Title

      J Thromb Haemost(peer reviewed) 5(1)

      Pages: 109-16

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] C-reactive protein induces high-mobility group box-1 protein release through activation of p38MAPK in macrophage RAW264.7 cells.2007

    • Author(s)
      Kawahara K, Biswas KK, Maruyama I, et. al.
    • Journal Title

      Cardiovasc Pathol. 17(3)

      Pages: 129-38

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HMGB1 release in co-cultures of porcine endothelial and human T cells2007

    • Author(s)
      Kawahara K, Setoyama K, Maruyama I and, et. al.
    • Journal Title

      Xenotransplantation. 14(6)

      Pages: 636-41

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HMGB1 expression by activated vascular smooth muscle cells in advanced human atherosclerosis plaques.2007

    • Author(s)
      Inoue K, Kawahara K, Maruyama I and, et. al.
    • Journal Title

      Cardiovasc Pathol. 16(3)

      Pages: 136-43

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High-mobility group box 1 protein promotes development of microvascular thrombosis in rats.2007

    • Author(s)
      Ito T, Maruyama I, et al.
    • Journal Title

      J Thromb Haemost. 5(1)

      Pages: 109-16

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cepharanthine triggers apoptosis in a human hepatocellular carcinoma cell line(HuH-7)through the activation of JNK1/2 and the downregulation of Akt2006

    • Author(s)
      Biswas KK, Hashiguchi T, Maruyama I, et. al.
    • Journal Title

      FEBS Letters 580(2)

      Pages: 703-10

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Endocannabinoid,anandamide in gingival tissue regulates the periodontal inflammation through NF-kappaB pathway inhibition2006

    • Author(s)
      Nakajima Y, Hashiguchi T, Maruyama I, et. al.
    • Journal Title

      FEBS Letters 580(2)

      Pages: 613-9

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Cepharanthine triggers apoptosis in a human hepatocellular carcinoma cell line(HuH-7) through the activation of JNK1/2 and the downregulation of Akt2006

    • Author(s)
      Biswas, KK., Hashiguchi, T., et. al.
    • Journal Title

      FEBS Letters(peer reviewed) 580(2)

      Pages: 703-10

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Endocannabinoid, anandamide in gingival tissue regulates the periodontal inflammation through NF-kappaB pathway inhibition2006

    • Author(s)
      Nakajima, Y., Hashiguchi, T., Maruyama, I., et. al.
    • Journal Title

      FEBS Letters(peer reviewed) 580(2)

      Pages: 613-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Cepharanthine triggers apoptosis in a human hepatocellular carcinoma cell line (HuH-7) through the activation of JNK1/2 and the downregulation of Akt.2006

    • Author(s)
      Biswas KK, Hashiguchi T, Maruyama I, et al.
    • Journal Title

      FEBS Letters 580(2)

      Pages: 703-710

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Endocannabinoid, anandamide in gingival tissue regulates the periodontal inflammation through NF-kappaB pathway inhibition.2006

    • Author(s)
      Nakajima Y, Hashiguchi T, Maruyama I, et al.
    • Journal Title

      FEBS Letters 580(2)

      Pages: 613-619

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Activated protein C,a natural anticoagulant protein,has antioxidant properties and inhibits lipid peroxidation and advanced glycation end products formation2005

    • Author(s)
      Yamaji K, Hashiguchi T, Maruyama I, et. al.
    • Journal Title

      Thrombosis Research 115(4)

      Pages: 319-25

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Inhibition of thrombin-induced vascular endothelial growth factor roduction in human neuroblastoma(NB-1)cells by argatroban2005

    • Author(s)
      Sarker KP, Hashiguchi T, aruyamaI, et. al.
    • Journal Title

      Pathophysiology of Haemostasis and Thrombosis 34(1)

      Pages: 41-7

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The N-terminal domain of thrombomodulin sequesters high mobility group-B1 protein,a novel anti-inflammatory mechanism2005

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

      J CIin Invest 115・5

      Pages: 1267-1274

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Activated protein C, a natural anticoagulant protein, has antioxidani properties and inhibits lipid peroxidation and advanced glycation end products formation2005

    • Author(s)
      Yamaji, K., Hashiguchi, T., Maruyama, I., et. al.
    • Journal Title

      Thrombosis Research(peer reviewed) 115(4)

      Pages: 319-25

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Inhibition of thrombin-induced vascular endothelial growth factor production in human neuroblastoma(NB-1) cells by argatroban2005

    • Author(s)
      Sarker, KP., Hashiguchi, T., Maruyama, I., et. al.
    • Journal Title

      Pathophysiology of Haemostasis and Thrombosis(peer reviewed) 34(1)

      Pages: 41-7

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The N-terminal domain of thrombomodulin sequesters high mobility group-B1 protein a novel anti-inflammatory mechanism2005

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

      J Clin Invest(peer reviewed) 115(5)

      Pages: 1267-1274

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 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, Hashiguchi T, Maruyama I, et al.
    • Journal Title

      Thrombosis Research 115(4)

      Pages: 319-325

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Inhibition of thrombin-induced vascular endothelial growth factor production in human neuroblastoma (NB-1) cells by argatroban.2005

    • Author(s)
      Sarker KP, Hashiguchi T, Maruyama I, et al.
    • Journal Title

      Pathophysiology of Haemostasis and Thrombosis 34(1)

      Pages: 41-47

    • 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., Maruyama, I., et al.
    • Journal Title

      J Clin Invest 115・5

      Pages: 1267-1274

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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