BET基因功能及其抑制剂在COPD中的作用  

Roles on the functions of BET genes and their inhibitors in COPD

作　　者：郭亮生 王帅 关程丹 高晓 吴斌 GUO Liangsheng;WANG Shuai;GUAN Chengdan;GAO Xiao;WU Bin(Guangdong Medical University,Zhanjiang 524000,China;Institute of Respiratory Diseases,Affiliated Hospital of Guangdong Medical University,Zhanjiang 524000,China;Department of Respiratory and Critical Care Medicine,Affiliated Hospital of Guangdong Medical University,Zhanjiang 524000,China)

机构地区：[1]广东医科大学,湛江524000 [2]广东医科大学附属医院呼吸疾病研究所,湛江524000 [3]广东医科大学附属医院呼吸与危重症医学科,湛江524000

出　　处：《生命的化学》2025年第4期633-645,共13页Chemistry of Life

基　　金：广东省基础与应用基础研究基金项目(2023A1515012298)。

摘　　要：溴结构域和额外末端结构域(bromodomain and extra-terminal domain,BET)蛋白家族通过其溴结构域特异性识别组蛋白上的乙酰化赖氨酸残基,调控基因表达。BET抑制剂通过阻断BET蛋白与组蛋白的相互作用,抑制炎症相关基因的表达,展现出显著的抗炎潜力。慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)是一种以慢性炎症和气流受限为特征的疾病,其发病机制复杂,涉及多种细胞因子和炎症细胞的相互作用。在COPD的病理过程中,BET蛋白家族成员[尤其是溴结构域蛋白4(bromodomain-containing protein 4,BRD4)]的异常激活与多种炎症信号通路密切相关。BET蛋白通过调控炎症相关基因的表达,推动气道炎症和气道重塑的进程。有研究表明,BET抑制剂能够显著减少炎症细胞因子的表达,抑制气道炎症和重塑,展现出在COPD治疗中的广阔应用前景。本文综述了BET蛋白家族的功能以及BET抑制剂在炎症性疾病,特别是COPD中的作用和研究进展。The bromodomain and extra-terminal domain(BET)protein family specifically recognizes acetylated lysine residues on histones through their bromodomains,thereby regulating gene expression.BET inhibitors block the interaction between BET proteins and histones,thereby suppressing the expression of inflammation-related genes and demonstrating significant anti-inflammatory potential.Chronic obstructive pulmonary disease(COPD)is characterized by chronic inflammation and airflow limitation,with a complex pathogenesis involving the interplay of various cytokines and inflammatory cells.During the pathogenesis of COPD,the abnormal activation of BET proteins,particularly bromodomain-containing protein 4(BRD4),is closely associated with multiple inflammatory signaling pathways.By regulating the expression of inflammation-related genes,BET proteins promote airway inflammation and remodeling.Studies have shown that BET inhibitors can significantly reduce the expression of inflammatory cytokines,inhibit airway inflammation and remodeling,and thus hold broad application prospects in the treatment of COPD.This work reviews the functions of the BET protein family and the role and research progress of BET inhibitors in inflammatory diseases,particularly COPD.

关 键 词：溴结构域和额外末端结构域 慢性阻塞性肺疾病 抗炎 抑制剂 

分 类 号：R563[医药卫生—呼吸系统]