Establishment and dynamism of des-HMGB1, degraded HMGB1 by thrombin-thrombomodulin

des-HMGB1、凝血酶-血栓调节蛋白降解的 HMGB1 的建立和动态

• 批准号: 23659491
• 负责人: MARUYAMA Ikuro
• 金额: $ 2.5万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659491/
• 关键词: 血栓; 止血学; トロンボモジュリン; トロンビン; HMGB1; DIC; des-HMGB1

We previously showed that HMGB1 binds to thrombomodulin(TM) and degraded by thrombin-TM at the N-terminus of the molecule cleaving out 10 aminoacdid-residue. We named this degraded HMGB1 as des-HMGB1. We also have showed that des-HMGB1 compete with intact binding to its receptor RAGE, Toll-like receptor-2 and-4 resulting negatively regulating of intact HMGB1 and its receptor signaling.In this study, we established the des-HMGB1 specific assay ELISA, and investigated its dynamism in various diseases including DIC, sepsis and shock. We showed that the des-HMGB1 was increased in the serum from the patients with these pathologic conditions, especially in the cases treated with recombinant TM. We are now further studying relationship between des-HMGB1 levels and the efficacy of TM treatment and their prognosis.

我们先前表明，HMGB1与血小板结合蛋白（TM）结合，并在分裂分裂的N端在分裂10氨基氧化物的N-末端降解。我们将此降级的HMGB1命名为DES-HMGB1。我们还表明，DES-HMGB1与其受体愤怒，Toll-like受体-2和-4的完整结合导致了完整的HMGB1及其受体信号的负调节。在这项研究中，我们建立了DES-HMGB1特异性分析ELISA，并在包括DIC，SEPIS和SEALP在内的各种疾病中调查了其动态性。我们表明，患有这些病理状况的患者的血清中DES-HMGB1增加了，尤其是在用重组TM治疗的病例中。现在，我们正在进一步研究DES-HMGB1水平与TM治疗的疗效及其预后之间的关系。