TXNIP公司
炎症体
小RNA
医学
关节炎
癌症研究
分泌物
发病机制
免疫学
下调和上调
细胞凋亡
细胞生物学
炎症
基因沉默
基因敲除
小干扰RNA
化学
内科学
氧化应激
生物化学
基因
硫氧还蛋白
作者
Xiaofeng Li,Wenwen Shen,Ying‐Yin Sun,Wanxia Li,Zhenghao Sun,Yan‐Hui Liu,Lei Zhang,Cheng Huang,Xiao‐Ming Meng,Jun Li
标识
DOI:10.1016/j.jbspin.2015.10.007
摘要
Rheumatoid arthritis (RA) is a heterogenic and systemic autoimmune disease characterized by synovitis and joint structural damage. However, the pathogenesis of RA is still obscure. It has been reported microRNA-20a (miRNA-20a) was significantly associated with the regulation of pro-inflammatory cytokines release in RA FLS. The purpose of this study was to explore the function and underlying mechanisms of miRNA-20a on NLRP3-inflammasome in adjuvant-induced arthritis (AA) fibroblast-like synoviocytes (FLSs) in vitro.In this study, using a combination of Western blotting, Q-PCR, and ELISA analysis, we investigated the influence and function of miRNA-20a on NLRP3-inflammasome by targeting TXNIP in AA FLSs.In the present study, the expression of NLRP3-inflammasome was significant up-regulated in AA model in vitro. Our study indicated that silence of NLRP3 down-regulated the expression of NLRP3-inflammasome and the secretion of IL-1β and MMP-1. Moreover, over-expression of miR-20a decreased formation of NLRP3-inflammasome, including NLRP3, ASC and caspase-1, and suppressed the secretion of IL-1β and MMP-1, along with down-regulated the expressions of TXNIP in primary FLSs isolated from AA. With the combined use of prediction programs and luciferase assay, the rat TXNIP mRNA 3'UTR predicted to be targeted by miR-20a. Similarly, inhibitor TXNIP expression by TXNIP-siRNA markedly repressed formation of NLRP3-inflammasome and the secretion of IL-1β and MMP-1.Taken together, these results indicate that miR-20a may play a pivotal role in the NLRP3-inflammasome by targeted inhibit TXNIP expression in AA FLSs.
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