芍药苷通过下调hsa_circ_009012抑制类风湿关节炎成纤维样滑膜细胞的炎症。
Paeoniflorin inhibits the inflammation of rheumatoid arthritis fibroblast-like synoviocytes by downregulating hsa_circ_009012.
作者信息
Yang Junping, Wei Zehong, Li Huaiyu, Lv Senhao, Fu Yong, Xiao Liang
机构信息
Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, 330006, Jiangxi, People's Republic of China.
Jiangxi University of Chinese Medicine, Nanchang, 330006, Jiangxi, People's Republic of China.
出版信息
Heliyon. 2024 May 1;10(9):e30555. doi: 10.1016/j.heliyon.2024.e30555. eCollection 2024 May 15.
BACKGROUND
Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to progressive joint damage. Circular RNA (circRNA) can regulate the inflammatory response of fibroblast-like synoviocytes (FLSs) in RA, influencing the disease progression. Paeoniflorin (PF) is the main active ingredient extracted from Paeonia lactiflora and is known for its anti-inflammatory effect. This study aims to explore the potential mechanisms by which hsa_circ_009012 and PF regulate the inflammatory response in RA.
METHODS
RNA expression of hsa_circ_009012, has-microRNA-1286 (miR-1286), toll-like receptor 4 (TLR4), NOD-like receptor thermal protein domain associated protein 3 (NLRP3) was assessed by real-time quantitative polymerase chain reaction (RT-qPCR) or western blotting (WB). Cell inflammation markers (TNF-α, IL-1β, IL-6) were assessed by RT-qPCR and immunofluorescence (IF). Counting Kit-8 (CCK-8) assay, flow cytometry, and transwell assay were utilized to test cell viability, cell cycle distribution, and migration.
RESULTS
Hsa_circ_009012 was highly expressed in RA-FLS. Hsa_circ_009012 over-expression facilitated the inflammation in RA-FLS and was closely associated with the miR-1286/TLR4 axis. Paeoniflorin inhibited inflammation and the expression of hsa_circ_009012 and TLR4, while upregulating the expression of miR-1286 in RA-FLS. Moreover, the upregulation of hsa_circ_009012 reversed the repressive effect of paeoniflorin on RA-FLS progression.
CONCLUSION
Paeoniflorin inhibits the inflammation of RA-FLS via mediating the hsa_circ_009012/miR-1286/TLR4/NLRP3 axis.
背景
类风湿关节炎（RA）是一种导致进行性关节损伤的慢性炎症性疾病。环状RNA（circRNA）可调节类风湿关节炎中滑膜成纤维样细胞（FLS）的炎症反应，影响疾病进展。芍药苷（PF）是从芍药中提取的主要活性成分，以其抗炎作用而闻名。本研究旨在探讨hsa_circ_009012和PF调节类风湿关节炎炎症反应的潜在机制。
方法
通过实时定量聚合酶链反应（RT-qPCR）或蛋白质免疫印迹法（WB）评估hsa_circ_009012、微小RNA-1286（miR-1286）、Toll样受体4（TLR4）、NOD样受体热蛋白结构域相关蛋白3（NLRP3）的RNA表达。通过RT-qPCR和免疫荧光（IF）评估细胞炎症标志物（肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6）。采用细胞计数试剂盒-8（CCK-8）法、流式细胞术和Transwell实验检测细胞活力、细胞周期分布和迁移。
结果
hsa_circ_009012在类风湿关节炎FLS中高表达。hsa_circ_009012过表达促进了类风湿关节炎FLS中的炎症反应，且与miR-1286/TLR4轴密切相关。芍药苷抑制炎症以及hsa_circ_009012和TLR4的表达，同时上调类风湿关节炎FLS中miR-1286的表达。此外，hsa_circ_009012的上调逆转了芍药苷对类风湿关节炎FLS进展的抑制作用。
结论
芍药苷通过介导hsa_circ_009012/miR-1286/TLR4/NLRP3轴抑制类风湿关节炎FLS的炎症反应。
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