高迁移率族蛋白1与心脏疾病的研究进展

Research advances in high mobility group protein 1 and its role in heart disease

高迁移率族蛋白1(high mobility group box protein 1,HMGB1)是一种非组蛋白核蛋白。HMGB1可以由细胞受到应激后主动分泌,也可由坏死细胞被动释放。在细胞核中HMGB1参与了DNA复制及调节转录等生理过程;当其在细胞外时,将作为损伤相关的分子模式(damage associated molecular patterns,DAMPs),通过与受体结合或细胞内吞等方式,对细胞的功能、增殖及炎症反应进行调控。研究发现,HMGB1在多种心脏疾病(包括冠心病、心衰、心脏缺血再灌注、心肌炎等)中发挥了不同的作用,但很多机制尚未明确阐述。本文就HMGB1的结构、生理学功能及其在心脏疾病中作用的研究进展进行综述,旨在阐述HMGB1在心脏疾病中的研究潜力。

High mobility group box protein 1(HMGB1)is a non-histone nuclear protein,which is passively released by necrotic tissues or actively secreted by stressed cells.In nucleus,HMGB1 is involved in transcription regulation,DNA replication and repair and nucleosome assembly.Extracellular HMGB1 acts as a damage-associated molecular pattern(DAMPs)molecule that promote a variety of cellular responses,including tissue inflammation or regeneration by binding to different receptors and endocytosis.HMGB1 plays different role in a variety of heart diseases(including coronary heart disease,heart failure,cardiac ischemia and reperfusion,myocarditis,etc.),while many mechanisms remain unexplored.This review summarizes recent findings on HMGB1 structure,biological function,and heart dysfunctions,and aims to discuss the research potential of HMGB1 in heart disease.