背景：HMGB1是一种细胞核蛋白，通常情况下以分子伴侣形式维持核小体的结构并调节基因转录。众多病理情况下，HMGB1可被免疫细胞和非免疫细胞释放到细胞外，进而促进多种慢性炎症和自身免疫疾病的发生。HMGB1有多种细胞膜受体，包括RAGE、 TLRs、Mac-1 、CD24等，可作用与多种类型细胞。 目的：在各种类型肺部疾病中，从临床研究到基础研究中，从急性期、慢性期到纤维化期全面探讨HMGB1的作用。 内容：本文总结了HMGB1相关信号通路在哮喘、肺纤维化、脓毒症与LPS相关急性肺损伤、休克相关肺损伤、机械通气相关肺损伤、细菌性肺炎及肺动脉高压疾病中的研究现状与结果。 趋向：在呼吸系统各种疾病模型中，从急性期、慢性期到纤维化期，HMGB1均参与其中。但机制研究方面，HMGB1通过哪种膜受体发挥主要作用，结果争议性较大, 是研究的热点。HMGB1的细胞靶点很广泛，但其不同疾病模型中通过哪种类型细胞起主要作用，研究结果差异较大。HMGB1相关通路中的关键蛋白分子，包括 HMGB1、RAGE受体和sRAGE等，动物研究表明它们的升高可能并不同步，其在人体水平的表达趋势与动物模型有一致性，但结果差异性较大，需加大样本量确切研究。HMGB1的特异性拮抗剂在动物水平有效，但在人体水平的研究还未有充分开展。
Background：HMGB1 is a nuclear protein that acts as a molecular chaperone and involves in the maintenance of nucleosome structure and regulation of gene transcription. It can be released to extracellular space from immune and non-immune cells in response to various stimuli. Extracellular HMGB1 contributes to the pathogenesis of numerous chronic inflammatory and autoimmune diseases. There are many kinds of receptors on cellular membrane, including RAGE,TLRs,Mac-1 ,CD24 and so on. What’s more, HMGB1 can stimulate various kinds of cell types. Objective：In various kinds of lung diseases, we tried to explore the role of HMGB1 from clinical research to basic research and from the acute stage to chronic fibrotic stage Content: We summarized the current research of HMGB1 mediated signal in asthma, pulmonary fibrosis, sepsis or LPS induced ALI(acute lung injury), shock, MV(mechanical ventilation), bacterial pneumonia and pulmonary hypertension disease. Trend: HMGB1 contributes to progression of various kinds of lung diseases from acute stage to chronic and fibrotic stage. But the results of its most functional receptors in different models and different cells are controversial and remains the research focus now. HMGB1 could target various types of cells, but which kind of cell plays the most important role in HMGB1 mediated different kind of disease is insufficient yet. The key proteins in HMGB1 related signal including HMGB1, RAGE and sRAGE always didn’t increase synchronously in animal studies, and their trends are sometimes not consistent to the clinical study, which needs larger clinical sample. Specific antagonist of HMGB1 in animal study has been proved effective, but its effectiveness in clinical study has not been fully carried out yet.
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