High-mobility group box protein 1 (HMGB1): an alarmin mediating the pathogenesis of rheumatic disease.
High-mobility group box protein 1 (HMGB1): an alarmin mediating the pathogenesis of rheumatic disease.
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DOI：
10.1186/ar2440
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发表时间：
2008
影响因子：
4.9
通讯作者：
Andersson, Ulf
中科院分区：
文献类型：
--
作者：
Pisetsky, David S.;Erlandsson-Harris, Helena;Andersson, Ulf
高迁移率族蛋白1（HMGB 1）是一种具有双重功能的非组蛋白核蛋白。在细胞内，HMGB 1结合DNA，调节转录并决定染色体结构。在细胞外，HMGB 1可以作为一种alarmin激活先天系统，并介导广泛的生理和病理反应。作为一种alarmin，HMGB 1从细胞核转移到细胞外环境，这一过程可以发生细胞活化以及细胞死亡。HMGB 1可与包括β 2受体（晚期糖基化终产物受体）以及Toll样受体-2（TLR-2）和TLR-4的受体相互作用，并与其他促炎介质以协同方式起作用以诱导反应。如对患者以及动物模型的研究所示，HMGB 1可以在风湿性疾病的发病机制中发挥重要作用，包括类风湿性关节炎、系统性红斑狼疮和多发性肌炎等。治疗这些疾病的新方法可能涉及抑制HMGB 1从细胞释放、其与受体的相互作用以及下游信号传导的策略。
High-mobility group box protein 1 (HMGB1) is a non-histone nuclear protein that has a dual function. Inside the cell, HMGB1 binds DNA, regulating transcription and determining chromosomal architecture. Outside the cell, HMGB1 can serve as an alarmin to activate the innate system and mediate a wide range of physiological and pathological responses. To function as an alarmin, HMGB1 translocates from the nucleus of the cell to the extra-cellular milieu, a process that can take place with cell activation as well as cell death. HMGB1 can interact with receptors that include RAGE (receptor for advanced glycation endproducts) as well as Toll-like receptor-2 (TLR-2) and TLR-4 and function in a synergistic fashion with other proinflammatory mediators to induce responses. As shown in studies on patients as well as animal models, HMGB1 can play an important role in the pathogenesis of rheumatic disease, including rheumatoid arthritis, systemic lupus erythematosus, and polymyositis among others. New approaches to therapy for these diseases may involve strategies to inhibit HMGB1 release from cells, its interaction with receptors, and downstream signaling.
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