Paeoniflorin Suppresses Rheumatoid Arthritis Development via Modulating the Circ-FAM120A/miR-671-5p/MDM4 Axis
Paeoniflorin Suppresses Rheumatoid Arthritis Development via Modulating the Circ-FAM120A/miR-671-5p/MDM4 Axis
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芍药苷通过调节 Circ-FAM120A/miR-671-5p/MDM4 轴抑制类风湿关节炎的发展
DOI：
10.1007/s10753-021-01504-0
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发表时间：
2021-08-23
期刊：
影响因子：
5.1
通讯作者：
Zheng, Fuzeng
中科院分区：
文献类型：
--
作者：
Ma, Junfu;Meng, Qingliang;Zheng, Fuzeng
芍药苷是从芍药中提取的活性成分，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。通过细胞计数试剂盒-8 （CCK-8）、流式细胞术和transwell实验评估细胞活力、周期分布、迁移和侵袭。采用酶联免疫吸附法（ELISA）检测炎症因子的含量。通过qRT-PCR和western blot检测RNA表达水平。通过双荧光素酶报告基因实验验证了miR-671-5p与circ-FAM120A （hsa_circ_0003972）或小鼠双分钟4 （MDM4）之间的靶向关系。芍药苷抑制类风湿关节炎成纤维细胞样滑膜细胞（RA- flss）的增殖、迁移、侵袭和炎症，加速细胞周期阻滞。Circ-FAM120A在RA滑膜组织和RA- flss中升高。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轴来减弱RA-FLS的进展。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，并触发细胞周期阻滞。
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.