摘要
高迁移率族蛋白B1(high mobility group protein B1,HMGB1)为主要存在于细胞核中与DNA结合的一种非组蛋白,具有多种核内功能。近年诸多研究发现,细胞外HMGB1作为一种重要的晚期炎性递质参与炎症免疫反应和肿瘤的生长、浸润、转移。HMGB1通过活化细胞的主动分泌和坏死损伤细胞的被动释放而进入细胞外,细胞外HMGB1可诱导单核/巨噬细胞、中性粒细胞、树突状细胞等表达分泌多种炎性递质。细胞外HMGB1与晚期糖基化终末产物受体、Toll样受体2、Toll样受体4等胞膜受体结合,激活丝裂原活化蛋白激酶、Janus激酶/信号转导和转录激活子、核转录因子-κB等信号转导通路而发挥其生物学效应。HMGB1靶向治疗将可能为炎症、癌症、氧化应激、无菌损伤等疾病开辟一个新的治疗途径。文中就HMGB1的结构和功能、细胞外分泌和释放、信号传导机制的研究进展作一综述。
High mobility group protein B1 （ HMGB1 ） is a DNA-binding nonhistone protein in the nucleus, with a variety of nu- clear functions. Recently, many researches have shown extracellular HMGB1, as an important late proinflammatory mediator, partici- pates in the inflammatory immune responses and the growth, invasion and metastasis of tumor. HMGB1 can be both actively secreted by active cells and passively released by necrotic/damaged ceils to the extracellular milieu. Extracellular HMGB1 can induce monocytes/ macrophages, neutrophils and dendritic cells to secrete various other proinflammatory mediators. It can bind membrane receptors such as RAGE, TLR2 and TLR4, and subsequently activate intracellular signal transduction pathways （ MAPKs, JAK/STAT, NF-kB） to exert its biological effects. HMGBl-targeting therapy may open a new treatment approach for inflammation, cancer, oxidative stress, sterile damage and related diseases. The paper will rewiew the research progress of the structure and function, extracellular secretion and release, and signal transduction mechanism of HMGB1.
出处
《医学研究生学报》
CAS
北大核心
2013年第3期296-299,共4页
Journal of Medical Postgraduates
基金
国家自然科学基金(81070074)
