Cellular mechanism in thrombin mediated HMGB1 release. Effect of cluster formation of HMGB1 on the cell-surface receptors.

凝血酶介导 HMGB1 释放的细胞机制。

• 批准号: 23390412
• 负责人: MARUYAMA Ikuro
• 金额: $ 12.06万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23390412/
• 关键词: PAMPｓ; DAMPｓ; HMGB1; inflammasome; トロンビン; PAR-1; NF-ｋB; TLR-2; TLR-4; シグナル伝達; 蛋白質; 糖尿病; 発現制御

HMGB1, a representative danger associated molecular patterns, DAMP is released from almost all nucleated necrotic cells and activated epithelial cells including endothelial cells. The HMGB1 released out of the cells acts on Toll Like receptors(TLR)-2,TLR-4 and receptor for advanced glycation endproducts, RAGE. If the cells were primed by preceding PAMPs, pathogen associated molecular patterns, dual signalings from PAMPs and DAMPs generate and secrete IL-1b(beta) and IL-18 resulting self-defensive inflammation and hemostatic reaction. However excessive this dual signaling often reads to systemic and/or fulminant inflammation and coagulation resulting systemic inflammatory response syndrome(SIRS) and/or disseminated intravascular coagulation(DIC). We could present that for example HMGB1 and LPS or thrombin may have a crucial role in these severe conditions. Thus the regulation and intervention of PAMPs and DAMPs are important in preventive medicine in the emergency medicines.

HMGB 1是一种典型的危险相关分子模式，DAMP从几乎所有的有核坏死细胞和活化的上皮细胞包括内皮细胞中释放。HMGB 1在细胞外释放，作用于Toll样受体（TLR）-2、TLR-4和晚期糖基化终产物受体（AGEs）。如果细胞被先前的PAMP、病原体相关的分子模式、来自PAMP和DAMP的双重信号转导引发，则产生并分泌IL-1b（β）和IL-18，导致自卫性炎症和止血反应。然而，过度的这种双重信号传导通常导致全身性和/或暴发性炎症和凝血，导致全身炎症反应综合征（SIRS）和/或弥散性血管内凝血（DIC）。我们可以提出，例如HMGB 1和LPS或凝血酶可能在这些严重的条件下起关键作用。因此，对PAMP和DAMP的调控和干预在急诊医学中的预防医学中具有重要意义。

项目成果

Valproic acid increases susceptibility to endotoxin shock through enhanced release o f high-mobility group box 1

丙戊酸通过增强高迁移率族盒 1 的释放来增加对内毒素休克的敏感性

• 发表时间: 2011
• 期刊: Shock
• 影响因子: 3.1
• 作者: Sugiura S;Maruyama I;Matsushita K.;et al
• 通讯作者: et al

Circulating high-mobility group box 1 and cardiovascular mortality in unstable angina and non-ST-segment elevation myocardial infarction

• DOI: 10.1016/j.atherosclerosis.2012.01.040
• 发表时间: 2012-04-01
• 期刊: ATHEROSCLEROSIS
• 影响因子: 5.3
• 作者: Hashimoto, Tousei;Ishii, Junnichi;Ozaki, Yukio
• 通讯作者: Ozaki, Yukio

Thrombomodulin : protectorate God of the vasculature in thrombosis and inflammation. J

血栓调节蛋白：血栓和炎症中脉管系统的保护神。

• 发表时间: 2011
• 期刊: Thromb Haemost
• 作者: Ito T;Maruyama I
• 通讯作者: Maruyama I

Gradual increase of high mobility group protein b1 in the lungs after the onset of acute exacerbation of idiopathic pulmonary fibrosis.

• DOI: 10.1155/2011/916486
• 发表时间: 2011
• 期刊: Pulmonary medicine
• 影响因子: 4.3
• 作者: Ebina M;Taniguchi H;Miyasho T;Yamada S;Shibata N;Ohta H;Hisata S;Ohkouchi S;Tamada T;Nishimura H;Ishizaka A;Maruyama I;Okada Y;Takashi K;Nukiwa T
• 通讯作者: Nukiwa T

Immunohistochemical expression of thrombomodulin in vestibular schwanoma

前庭神经鞘瘤中血栓调节蛋白的免疫组织化学表达

• 发表时间: 2013
• 期刊: Brain Tumor Pathol
• 影响因子: 3.3
• 作者: Yamahata;H
• 通讯作者: H