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Paeoniflorin Suppresses Rheumatoid Arthritis Development via Modulating the Circ-FAM120A/miR-671-5p/MDM4 Axis

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Abstract

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.

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The data that support the findings of this study are available on request from the corresponding author.

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Funding

This work was supported by the National Natural Science Foundation of China Youth Project (No. 81804050) and Key Subject of Henan Province Traditional Chinese Medicine Scientific Research Project (No. 2018ZY1011).

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Author notes

  1. Junfu Ma and Qingliang Meng These authors contributed equally to this paper.

Authors and Affiliations

  1. Department of Rheumatology, Henan Province Hospital of Traditional Chinese Medicine (The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine), Henan University of Traditional Chinese Medicine, Henan Province, Zhengzhou City, China

    Junfu Ma, Qingliang Meng, Junping Zhan, Huilian Wang, Wei Fan & Fuzeng Zheng

  2. Henan Province Hospital of Traditional Chinese Medicine (The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine), Henan University of Traditional Chinese Medicine, Henan Province, Zhengzhou City, China

    Yanqi Wang & Sudan Zhang

  3. Zhang Zhongjing College of Chinese Medicine, Nanyang Institute of Technology, Henan Province, Nanyang City, China

    Hua Bian

  4. Department of Rheumatology, Henan Province Hospital of Traditional Chinese Medicine (The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine), Henan University of Traditional Chinese Medicine, Zhengzhou City, Henan Province, China

    Fuzeng Zheng

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  1. Junfu Ma
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Contributions

Junfu Ma had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Junfu Ma, Qingliang Meng, Junping Zhan, Huilian Wang, and Wei Fan; acquisition of data: Yanqi Wang, Sudan Zhang, Hua Bian, and Fuzeng Zheng; critical revision of the manuscript for important intellectual content: Junfu Ma; administrative, technical, or material support: Junfu Ma, Qingliang Meng, and Junping Zhan; study supervision: Junfu Ma.

Corresponding author

Correspondence to Fuzeng Zheng.

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Written informed consent was obtained from patients with approval by the Institutional Review Board in Henan Province Hospital of Traditional Chinese Medicine.

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Ma, J., Meng, Q., Zhan, J. et al. Paeoniflorin Suppresses Rheumatoid Arthritis Development via Modulating the Circ-FAM120A/miR-671-5p/MDM4 Axis. Inflammation 44, 2309–2322 (2021). https://doi.org/10.1007/s10753-021-01504-0

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