miR-124a inhibits the proliferation and inflammation in rheumatoid arthritis fibroblast-like synoviocytes via targeting PIK3/NF-κB pathway
miR-124a inhibits the proliferation and inflammation in rheumatoid arthritis fibroblast-like synoviocytes via targeting PIK3/NF-κB pathway
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miR-124a通过靶向PIK3/NF-kappa B通路抑制类风湿关节炎成纤维样滑膜细胞的增殖和炎症
DOI：
10.1002/cbf.3386
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发表时间：
2019-06-01
影响因子：
3.6
通讯作者：
Tian, Jing
中科院分区：
文献类型：
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作者：
Yang, BiLing;Ge, Yan;Tian, Jing
成纤维细胞样滑膜细胞(FLS)的异常增殖导致类风湿关节炎(RA)的进展。本研究旨在探讨miR-124A在类风湿关节炎发病机制中的作用。用细胞计数试剂盒8和流式细胞仪检测类风湿关节炎(RAFLS)中FLS的活性和细胞周期。实时定量聚合酶链式反应和Western印迹分析检测PIK3CA、Akt和NF-kappa B在RAFLS中的表达。用酶联免疫吸附试验检测肿瘤坏死因子-α和白介素6的产生。采用组织学和免疫组织化学方法观察胶原性关节炎(CIA)小鼠的关节肿胀和炎症反应。我们发现miR-124A抑制RAFLS的存活和增殖，并增加细胞处于G1期的百分比。MIR-124A抑制PIK3CA 3‘UTR型荧光素酶报告基因活性，降低PIK3CA在mRNA和蛋白水平的表达。此外，miR-124A抑制PIK3/Akt/NF-kappa B信号通路的关键成分的表达，并抑制促炎因子TNF-α和IL-6的表达。CIA小鼠关节局部过表达miR-124A通过降低PIK3CA的表达，抑制炎症反应，促进FLS的凋亡。结论：miR-124A通过靶向PIK3/NF-kappa B途径抑制RAFLS的增殖和炎症反应。MIR-124A是治疗RA的有前景的靶点。
Abnormal hyperplasia of fibroblast-like synoviocytes (FLS) leads to the progression of rheumatoid arthritis (RA). This study aimed to investigate the role of miR-124a in the pathogenesis of RA. The viability and cell cycle of FLS in rheumatoid arthritis (RAFLS) were evaluated by Cell Counting Kit 8 and flow cytometry assay. The expression of PIK3CA, Akt, and NF-kappa B in RAFLS was examined by real-time PCR and Western blot analysis. The production of tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 was detected by ELISA. The joint swelling and inflammation in collagen-induced arthritis (CIA) mice were examined by histological and immunohistochemical analysis. We found that miR-124a suppressed the viability and proliferation of RAFLS and increased the percentage of cells in the G1 phase. miR-124a suppressed PIK3CA 3'UTR luciferase reporter activity and decreased the expression of PIK3CA at mRNA and protein levels. Furthermore, miR-124a inhibited the expression of the key components of the PIK3/Akt/NF-kappa B signal pathway and inhibited the expression of pro-inflammatory factors TNF-alpha and IL-6. Local overexpression of miR-124a in the joints of CIA mice inhibited inflammation and promoted apoptosis in FLS by decreasing PIK3CA expression. In conclusion, miR-124a inhibits the proliferation and inflammation in RAFLS via targeting PIK3/NF-kappa B pathway. miR-124a is a promising therapeutic target for RA.