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miR-483-3p Promotes IL-33 Production from Fibroblast-Like Synoviocytes by Regulating ERK Signaling in Rheumatoid Arthritis

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Abstract

Our previous studies have identified miR-483-3p to be highly expressed in synoviocytes from patients with rheumatoid arhtirits (RA); however, its effects on inflammation of RA fibroblast-like synoviocytes (FLSs) have remained unclear. The expression of miR-483-3p and cytokines in RA FLSs was detected using quantitative real-time polymerase chain reaction. Enzyme-linked immunosorbent was conducted to determine interleukin (IL)-33 production from RA FLSs. Western blotting was employed to quantify the levels of p-ERK and total ERK. Overexpressed miR-483-3p significantly increased the mRNA and protein expression of IL-33, but not of IL-27 or IL-34, in RA FLSs, whereas miR-483-3p suppression showed the opposite effects. Furthermore, miR-483-3p upregulation activated the ERK signaling pathway. The ERK signaling inhibitor PD98059 partly reversed the elevation of IL-33 levels mediated by miR-483-3p overexpression. Our results reveal that miR-483-3p promotes IL-33 expression by regulating the ERK signaling pathway in RA FLSs. Thus, miR-483-3p may be a potential effective target for RA treatment.

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Funding

This study was supported by grants from the Faculty Post-doctoral Research Startup Fund of China Medical University (No.M0470 to Yuejiao Wang) and the 345 Talent Project of Shengjing Hospital of China Medical University (No.M0686 to Yuejiao Wang).

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YW: conception and design of the research; KZ: acquisition of data and drafting the manuscript; KZ, TJ, and SZ: analysis and interpretation of data; DW: statistical analysis; WF and YW: revision of manuscript for important intellectual content. All authors contributed to data analysis, drafting and revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

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Correspondence to YueJiao Wang.

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This study was performed according to the recommendations of the Declaration of Helsinki and approved by the Ethics Committee of Shengjing Hospital of China Medical University (2019PS637K).

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Zhang, K., Fu, W., Zhao, S. et al. miR-483-3p Promotes IL-33 Production from Fibroblast-Like Synoviocytes by Regulating ERK Signaling in Rheumatoid Arthritis. Inflammation 44, 2302–2308 (2021). https://doi.org/10.1007/s10753-021-01503-1

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