The role of NLRP3/GATA-4/VEGF signal pathway in neovascular age-related macular degeneration
10.3760/cma.j.cn431274-20230308-00315
- VernacularTitle: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
- Author:
Luping WANG
1
;
Youjing ZHANG
;
Hao WANG
;
Lingge SUO
;
Ran YOU
Author Information
1. 首都医科大学附属北京友谊医院眼科，北京 100050
- Keywords:
Macular degeneration;
Choroidal neovascularization;
Vascular endothelial growth factor;
NLR family, pyrin domain-containing 3 protein;
GATA4 transcription
- From:
Journal of Chinese Physician
2023;25(4):486-490
- CountryChina
- Language:Chinese
-
Abstract:
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.
