巨噬细胞中YAP协同NF-κBp65激活NLRP3炎症小体促进M1型极化  

YAP in macrophages cooperates with NF-κBp65 to activate NLRP3 inflammasome and promote M1 polarization

作　　者：郑美佳 贾瑞 闫曙光[1,2] 魏海梁 李京涛 ZHENG Mei-jia;JIA Rui;YAN Shu-guang;WEI Hai-liang;LI Jing-tao(Teaching and Research Department of Prescriptions,School of Basic Medicine,Shaanxi University of Traditional Chinese Medicine,Xianyang 712046,China;Key Research Laboratory of Traditional Chinese Medicine for Gastrointestinal Conditions,Shaanxi University of Traditional Chinese Medicine,Xianyang 712046,China;Department of General Surgery,Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine,Xianyang 712000,China;Department of Infectious Diseases,Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine,Xianyang 712000,China)

机构地区：[1]陕西中医药大学基础医学院方剂学教研室,咸阳712046 [2]陕西中医药大学胃肠病证方药重点研究室,咸阳712046 [3]陕西中医药大学附属医院普外科,咸阳712000 [4]陕西中医药大学附属医院感染科,咸阳712000

出　　处：《现代免疫学》2023年第3期233-238,244,共7页Current Immunology

基　　金：国家自然科学基金(81403320,81873233);陕西中医药大学学科创新团队建设项目(2019-YL-05)。

摘　　要：炎症性肠病(inflammatory bowel disease, IBD)是一种慢性非特异性炎性疾病,同时也是一种自身免疫性疾病,巨噬细胞作为固有免疫细胞在其中发挥至关重要的作用。Yes相关蛋白(Yes-associated protein, YAP)是Hippo信号通路的关键蛋白。之前有研究显示,YAP在肠上皮细胞中具有促进细胞增殖修复并减轻IBD的功能。但最近研究显示,巨噬细胞中YAP可通过促进M1型极化加重IBD,而YAP缺乏可导致M2型极化并减轻IBD。近年,关于巨噬细胞中YAP的研究层出不穷,但YAP在巨噬细胞中调控极化的机制尚不完全清楚。最近的研究发现,巨噬细胞中YAP可协同NF-κBp65激活NOD样受体家族含pyrin结构域蛋白3(NOD-like receptor family pyrin domain-containing protein 3, NLRP3)炎症小体,参与M1型巨噬细胞极化的促炎反应。该文对巨噬细胞中YAP协同NF-κBp65激活NLRP3炎症小体,促进M1型极化,加重IBD的研究进展以及巨噬细胞中YAP靶点的治疗前景予以综述。Inflammatory bowel disease(IBD)is a nonspecific chronic inflammatory disease as well as an autoimmune disease.Innate immune cell macrophage plays an important role in the pathogenesis of this disease.Yes-associated protein(YAP)is the key protein of Hippo signaling pathway.YAP has been reported to promote proliferation and repair intestinal epithelial cells thus alleviating IBD.However,recent studies have shown that YAP in macrophages aggravates IBD by promoting M1 polarization and that YAP deficiency leads to M2 polarization and IBD alleviation.In recent years,though studies on YAP in macrophages are numerous,the mechanism of YAP regulating polarization in macrophages is yet to be elucidated.Recent studies revealed that YAP in macrophages cooperated with NF-κBp65 to activate NOD-like receptor family pyrin domain-containing protein 3(NLRP3)inflammasome and participated in the pro-inflammatory response of M1 macrophage polarization.This review outlines the current developments of YAP functions in macrophages,including its cooperation with NF-κBp65 to activate NLRP3 inflammasome,the regulation of TAP on M1 polarization and IBD,and the therapeutic prospect of targeting YAP in macrophages.

关 键 词：炎症性肠病 Yes相关蛋白 核因子κB p65蛋白 NOD样受体家族含pyrin结构域蛋白3 巨噬细胞极化 

分 类 号：R392.32[医药卫生—免疫学]