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Silence of S1PR4 Represses the Activation of Fibroblast-like Synoviocytes by Regulating IL-17/STAT3 Signaling Pathway

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Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease with persistent inflammation and progressive joint damage. However, the underlying pathological mechanisms of RA are still unclear. Fibroblast‑like synoviocytes (FLSs) play an important role in the pathogenesis of RA by the regulation of proliferation and apoptosis, and the release of multiple pro-inflammatory factors. The lipid mediator sphingosine-1-phosphate receptor 4 (S1PR4) is one of the sphingolipid sphingosine-1-phosphate (S1P) receptors, which affects the function of immune cells. However, the role of S1PR4 in the activation of FLSs and the development of RA is unknown. In this study, we found that the expression of S1PR4 was significantly increased in RA-FLSs. The silence of S1PR4 decreases the proliferation, migration, proinflammation, and promotes the apoptosis of RA-FLSs, accompanied with repressing interleukin-17 (IL-17)/signal transducer and activator of transcription 3 (STAT3) signal pathway. However, the regulatory effects of S1PR4 silencing on RA-FLSs were partly abolished by additional recombinant human (rh) IL-17A treatment. Therefore, our study demonstrated that S1PR4 silencing might inhibit proliferation, migration, proinflammation, and promote apoptosis of RA-FLSs partly by repressing IL-17, which suggests that inhibitors for S1PR4 might be a potentially promising strategy for the treatment of RA.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Nephropathy and Rheumatism, Tongde Hospital of Zhejiang Province, Hangzhou, 310007, Zhejiang, China

    Pengyu Zhang

  2. Department of Rheumatology and Immunology, The 962Nd Hospital of The PLA Joint Logistic Support Force, Harbin, Heilongjiang, 150080, China

    Qiang Zhang

  3. Department of Gynaecology, Shaoxing Second Hospital, No. 123 Yan’an Road, Shaoxing, 312000, Zhejiang, China

    Zhenxia Shao

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  1. Pengyu Zhang
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ZS designed the study. PZ and QZ conducted the experiments, collected and analyzed the data. PZ wrote the manuscript. ZS revised the manuscript. All authors reviewed the manuscript.

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Correspondence to Zhenxia Shao.

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Zhang, P., Zhang, Q. & Shao, Z. Silence of S1PR4 Represses the Activation of Fibroblast-like Synoviocytes by Regulating IL-17/STAT3 Signaling Pathway. Inflammation 46, 234–243 (2023). https://doi.org/10.1007/s10753-022-01728-8

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  • DOI: https://doi.org/10.1007/s10753-022-01728-8

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