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Paeoniflorin Suppresses Rheumatoid Arthritis Development via Modulating the Circ-FAM120A/miR-671-5p/MDM4 Axis
Inflammation ( IF 4.5 ) Pub Date : 2021-08-23 , DOI: 10.1007/s10753-021-01504-0
Junfu Ma 1 , Qingliang Meng 1 , Junping Zhan 1 , Huilian Wang 1 , Wei Fan 1 , Yanqi Wang 2 , Sudan Zhang 2 , Hua Bian 3 , Fuzeng Zheng 1, 4
Affiliation  

Paeoniflorin is an active ingredient derived from Paeonia, which has an anti-inflammatory effect. However, the potential role and basis of paeoniflorin in rheumatoid arthritis (RA) are indistinct. Cell viability, cycle distribution, migration, and invasion were evaluated via Cell Counting Kit-8 (CCK-8), flow cytometry, and transwell assays. The contents of inflammatory cytokines were examined using enzyme-linked immunosorbent assay (ELISA). RNA expression levels were determined via qRT-PCR and western blot. The targeting relationship between miR-671-5p and circ-FAM120A (hsa_circ_0003972) or murine double minute 4 (MDM4) was validated via dual-luciferase reporter assay. Paeoniflorin restrained proliferation, migration, invasion, and inflammation and accelerated cell cycle arrest in RA fibroblast–like synoviocytes (RA-FLSs). Circ-FAM120A was boosted in RA synovial tissues and RA-FLSs. Circ-FAM120A upregulation, miR-671-5p knockdown, or MDM4 augmentation reversed the repressive effect of paeoniflorin on RA-FLS progression. Moreover, paeoniflorin attenuated RA-FLS progression by regulating the circ-FAM120A/miR-671-5p/MDM4 axis. Paeoniflorin inhibited RA-FLS proliferation, mobility, and inflammation and triggered cell cycle arrest via mediating the circ-FAM120A/miR-671-5p/MDM4 pathway.



中文翻译:

芍药苷通过调节 Circ-FAM120A/miR-671-5p/MDM4 轴抑制类风湿性关节炎的发展

芍药甙是一种源自芍药的活性成分,具有抗炎作用。然而,芍药苷在类风湿关节炎(RA)中的潜在作用和基础尚不清楚。通过 Cell Counting Kit-8 (CCK-8)、流式细胞术和 transwell 分析评估细胞活力、循环分布、迁移和侵袭。采用酶联免疫吸附试验(ELISA)检测炎性细胞因子的含量。通过 qRT-PCR 和蛋白质印迹测定 RNA 表达水平。通过双荧光素酶报告基因分析验证了 miR-671-5p 与 circ-FAM120A (hsa_circ_0003972) 或小鼠双分钟 4 (MDM4) 之间的靶向关系。芍药苷可抑制 RA 成纤维细胞样滑膜细胞 (RA-FLS) 的增殖、迁移、侵袭和炎症,并加速细胞周期停滞。Circ-FAM120A 在 RA 滑膜组织和 RA-FLS 中得到增强。Circ-FAM120A 上调、miR-671-5p 敲低或 MDM4 增强逆转了芍药苷对 RA-FLS 进展的抑制作用。此外,芍药苷通过调节 circ-FAM120A/miR-671-5p/MDM4 轴减弱 RA-FLS 进展。芍药苷通过介导 circ-FAM120A/miR-671-5p/MDM4 通路抑制 RA-FLS 增殖、迁移和炎症,并触发细胞周期停滞。

更新日期:2021-08-24
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