Spatiotemporal spread of inflammation caused by HMGB1 nuclear DNA-binding protein

HMGB1 核 DNA 结合蛋白引起的炎症时空扩散

• 批准号: 23790447
• 负责人: OYAMA Yoko
• 金额: $ 2.75万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23790447/
• 关键词: High mobility group box-1 protein; RAGE; TLR2; TLR4; Thrombomodulin; Reactive oxygen species; HMGB1; 肉芽腫性腎炎

High-mobility group box-1 protein (HMGB1) was originally described as a nuclear DNA-binding protein that facilitates gene transcription by stabilizing nucleosome formation. HMGB1 can also be released or secrete extracellularly from cells as a result of cellular necrosis or activated macrophages/monocytes in response to inflammatory stimuli respectively, and acts as a pro-inflammatory cytokine or alarm signal for tissue damage. We have revealed that HMGB1 can trigger a potent inflammatory response and accelerates granulomatous inflammation leading to severe tissue injury. In this study, we tried to disclose further mechanism of HMGB1- associated granulomatous inflammation. From a point of view that controlling HMGB1 is essential for treatment of granulomatous nephritis, we studied experiments using a granulomatous nephritis animal model to investigate follows;1． The relationship between degrees of the nephritis and HMGB1 receptors expression2． The effect of anti-HMGB1 antibody3． TM association of the nephritis4． Reactive oxygen species association of the nephritisWe have found that receptors of HMGB1 and TM could be a target for inhibiting granulomatous nephritis.

高迁移率族蛋白1（HMGB 1）最初被描述为核DNA结合蛋白，通过稳定核小体的形成促进基因转录。HMGB 1还可以分别作为响应于炎性刺激的细胞坏死或活化的巨噬细胞/单核细胞的结果从细胞中释放或分泌到细胞外，并充当促炎细胞因子或组织损伤的警报信号。我们已经发现，HMGB 1可以引发强有力的炎症反应，并加速肉芽肿性炎症，导致严重的组织损伤。本研究试图进一步揭示HMGB 1相关性肉芽肿性炎症的机制。从控制HMGB 1对于治疗肉芽肿性肾炎是必要的观点出发，我们使用肉芽肿性肾炎动物模型进行了实验研究，以研究以下内容：1. HMGB 1受体表达与肾脏病变程度的关系2.抗HMGB 1抗体的作用3.肾炎的TM相关性4.我们发现HMGB 1和TM的受体可能是抑制肉芽肿性肾炎的靶点。