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BAFF Promotes FLS Activation Through BAFFR-Mediated Non-canonical NF-κB Pathway and the Effects of CP-25

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Abstract

B cell activating factor (BAFF) has been shown to play a key role in regulating B cell function, but little is known about whether BAFF affects the function of fibroblast-like synoviocyte (FLS), an effector cell of rheumatoid arthritis (RA). CP-25, a new ester derivative of paeoniflorin, could alleviate the arthritis symptoms of collagen-induced arthritis (CIA) mice by inhibiting BAFF-mediated abnormal activation of B cells. In this study, we aimed to understand the mechanism by which BAFF activates FLS and the effect of CP-25 on FLS function. Therefore, the proliferation and migration abilities of FLS and key proteins on the non-canonical NF-κB pathway were examined. The results showed that compared with the FLS of normal rats/OA patients, the expression of BAFF-R, TRAF2, NIK, p-IKKα, P100, and P52 was higher in the FLS of AA rats/RA patients, while the expression of TRAF3 was lower. And, BAFF promotes FLS activation by activating the non-canonical NF-κB signaling pathway. Meanwhile, BAFFR-siRNA inhibited the proliferation of FLS and the activation of non-canonical NF-κB signaling in FLS induced by BAFF. Additionally, CP-25 could inhibit abnormal proliferation and migration of FLS by regulating non-canonical NF-κB signaling. We concluded that BAFF may act as an important role in facilitating the function of FLS through the BAFFR-mediated non-canonical NF-κB pathway, which would be useful for revealing the pathological mechanism of RA. And CP-25 may become a potential new drug for the treatment of RA, providing a scientific basis for the development of new drugs to treat RA.

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DATA AVAILABILITY

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

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Funding

This work was supported by the National Natural Science Foundation of China (U1803129) and the Key Research and Development Plan of Anhui Province in 2021-Population Health Project (202104j07020032).

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Author notes

  1. Han Wang, Dan Mei, Fa-qin Liang, Zi-yang Xue, Pan Wang, and Rui-jin Liu are co-first authors and contributed equally to this manuscript.

Authors and Affiliations

  1. Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Centre of Anti-Inflammatory and Immune Medicine, Center of Rheumatoid Arthritis of Anhui Medical University, Hefei, 230032, China

    Han Wang, Dan Mei, Fa-qin Liang, Zi-yang Xue, Pan Wang, Rui-jin Liu, Yu-chen Zhao, Lin Jin, Zi-wei Zhang, Yuan-fang Zhai, Xian-zheng Zhang, Wei Wei & Ling-ling Zhang

  2. Department of Oncology, The First Affiliated Hospital, Institute for Liver Diseases of Anhui Medical University, Hefei, 230032, China

    Xian-zheng Zhang

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Contributions

Han Wang, Dan Mei, Fa-qin Liang, Zi-yang Xue, Pan Wang, and Rui-jin Liu conducted most experiments, analyzed data, and wrote manuscripts. Yu-chen Zhao, Lin Jin, Zi-wei Zhang, Yuan-fang Zhai, and Xian-zheng Zhang conducted some experiments. Pro. Wei Wei, and Ling-ling Zhang provided knowledge for the design and conduct of the experiment, data processing, and manuscript writing. The manuscript has been reviewed and approved by all authors.

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Correspondence to Ling-ling Zhang.

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All experiments were performed according to the Ethics Review Committee of Anhui Medical University (No.2018003 and No. LLSC2018007).

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Wang, H., Mei, D., Liang, Fq. et al. BAFF Promotes FLS Activation Through BAFFR-Mediated Non-canonical NF-κB Pathway and the Effects of CP-25. Inflammation 46, 861–875 (2023). https://doi.org/10.1007/s10753-022-01774-2

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