遵义医科大学学报2025,Vol.48Issue(3):252-262,269,12.
BMSCs来源的外泌体miR-515-5p可下调TLR4/NLRP3通路抑制RA-FLS
BMSCs-derived exosome miR-515-5 p down-regulates the TLR4/NLRP3 path-way to inhibit synovioblast-like cells
摘要
Abstract
Objective To explore the effect of the TLR4/NLRP3 pathway mediated by exosome miR-515-5p of bone marrow mesenchymal stem cells(BMSCs)on the proliferation,apoptosis,migration,and invasion of syno-vioblast-like cells(RA-FLS)in rheumatoid arthritis.Methods BMSCs and RA-FLS cells were cultured in vitro to prepare BMSCs with low expression of miR-515-5p and RA-FLS cells transfected with si-TLR4.RA-FLS cells and transfected cells were divided into 4 groups:RA-FLS control,RA-FLS+exosome treatment group,RA-FLS+miR-515-5p inhibitor exosome treatment group,si-TLR4 transfected RA-FLS cells+miR-515-5p inhibi-tor exosome treatment group.EDU,CCK-8,flow apoptosis,scratch test,Transwell,ELISA and Western blot were performed to detect biological changes.Results In the BMSCs exosome group,miR-515-5p significantly in-hibited the proliferation and apoptosis of RA-FLS cells,suppressed their invasion,migration,and the release of inflammatory cytokines such as IL-6,TNF-α,and IL-1β,and downregulated the expression of TLR4 and NLRP3 proteins.Upon inhibition of miR-515-5p,the expression levels of TLR4 and NLRP3 proteins in RA-FLS cells were upregulated;however,this upregulation is not observed in RA-FLS cells transfected with Si-TLR4.Conclusion BMSCs cell-derived exosome miR-515-5p inhibits the proliferation,migration,invasion and release of inflammatory factors of RA-FLS cells,and promotes their apoptosis by targeting down-regulation of the TLR4/NLRP3 pathway.关键词
骨髓间充质干细胞/外泌体/miR-515-5p/TLR4/NLRP3/RA-FLSKey words
bone marrow mesenchymal stem cells/exosome/miR-515-5p/TLR4/NLRP3/RA-FLS分类
临床医学引用本文复制引用
蔡东峰,钟超,杨子肖,李继模,张靖,洪嵩..BMSCs来源的外泌体miR-515-5p可下调TLR4/NLRP3通路抑制RA-FLS[J].遵义医科大学学报,2025,48(3):252-262,269,12.基金项目
贵州省科技厅基础研究计划项目[NO:黔科合基础-ZK(2023)一般542] (2023)
贵州省卫健委科技基金资助项目(NO:gzwjk2020-1-127). (NO:gzwjk2020-1-127)