NLRP3/GATA-4/VEGF信号通路在新生血管性年龄相关性黄斑变性中的作用  

The role of NLRP3/GATA-4/VEGF signal pathway in neovascular age-related macular degeneration

作　　者：王露萍 张佑靖 王皓 索玲格 尤冉 Wang Luping;Zhang Youjing;Wang Hao;Suo Lingge;You Ran(Department of Ophthalmology,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China;Department of Clinical Epidemiology and Evidence-Based Medicine,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China;Department of Ophthalmology,Peking University Third Hospital,Beijing 100191,China;Beijing Key Laboratory of Restoration of Damaged Ocular Nerve,Beijing 100191,China)

机构地区：[1]首都医科大学附属北京友谊医院眼科,北京100050 [2]首都医科大学附属北京友谊医院临床流行病学与循证医学研究室,北京100050 [3]北京大学第三医院眼科,北京100191 [4]眼部神经损伤的重建保护与康复北京市重点实验室,北京100191

出　　处：《中国医师杂志》2023年第4期486-490,共5页Journal of Chinese Physician

基　　金：国家自然科学基金(82000899)。

摘　　要：目的探讨核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)/转录因子GATA结合蛋白4(GATA-4)/血管内皮生长因子(VEGF)信号通路在新生血管性年龄相关性黄斑变性(nAMD)中的作用。方法利用TRANSFAC转录因子数据库搜索人源和鼠源VEGF启动子及其上游序列,分析可能影响VEGF转录活性的转录因子。将小鼠巨噬细胞RAW264.7分为对照组和脂多糖(LPS)刺激组,qRT-PCR检测LPS对NLRP3炎症小体活化、GATA-4和血管内皮生长因子A(VEGFA)mRNA表达的影响;应用特异性NLRP3小分子抑制剂MCC950预处理RAW264.7细胞(LPS+MCC950组),检测NLRP3、Caspase-1、IL-1β、GATA-4和VEGFA基因表达水平的变化。结果人源和鼠源VEGF启动子上游均存在多个GATA转录因子结合位点。与对照组比较,LPS组NLRP3、Caspase-1、IL-1β、GATA-4和VEGFA mRNA表达增加(均P<0.05);与LPS刺激组比较,LPS+MCC950组NLRP3、Caspase-1、IL-1β、GATA-4和VEGFA mRNA水平均明显降低(均P<0.05)。结论NLRP3/GATA-4/VEGF信号通路可能在nAMD的病理过程中发挥重要调节作用。Objective To explore the potential role of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/GATA-binding protein 4(GATA-4)/vascular endothelial growth factor(VEGF)signal pathway in neovascular age-related macular degeneration(nAMD).Methods We applied the TRANSFAC Public database to search the human and mouse VEGF promoters and upstream transcription factors,analyzed the transcription factors that may influence the transcriptional activity of VEGF.The RAW264.7 cells were divided into control group and lipopolysaccharide(LPS)stimulated group(LPS group).Real time fluorescence quantitative polymerase chain reaction(qRT-PCR)was used to detect the activation of NLRP3 inflammasome,and the mRNA levels of GATA-4 and VEGFA.Thus,we applied the specific small molecular NLRP3 inhibitor MCC950 pretreated RAW264.7 cells(LPS+MCC950 group),and detected the gene expression of NLRP3,Caspase-1,interleukin 1β(IL-1β),GATA-4 and VEGFA.Results There were multiple GATA transcription factor binding sites upstream of human and mouse VEGF promoters.Compared with the control group,mRNA expression of NLRP3,Caspase-1,IL-1β,GATA-4 and VEGFA in LPS group were increased(all P<0.05).Compared with LPS group,mRNA expression of NLRP3,Caspase-1,IL-1β,GATA-4 and VEGFA in LPS+MCC950 group were significantly decreased(all P<0.05).Conclusions NLRP3/GATA-4/VEGF signal pathway may play a significant role in the pathologic processes of nAMD.

关 键 词：黄斑变性 脉络膜新生血管化 血管内皮生长因子 NLR家族 热蛋白结构域包含蛋白3 GATA4转录因子 

分 类 号：R774.5[医药卫生—眼科]