2005 Fiscal Year Final Research Report Summary
Newly development of functional low molecular therapeutics : Study of the pathomechanism of lethal multiple organ failure
| Project/Area Number |
16390516
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Emergency medicine
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| Research Institution | Kagoshima University |
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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)
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| 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)
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| Project Period (FY) |
2004 – 2005
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| Keywords | HMGB1 / thrombomodulin / sepsis / DIC / lethality / anti-inflammatory peptide |
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| 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.
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Research Products
(14 results)
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[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.
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Journal Title
J Clin Invest. 115(5)
Pages: 1267-1274
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Thromb Res. 115(4)
Pages: 319-325
Description
「研究成果報告書概要(欧文)」より
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[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.
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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
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