Mir-223-3p And Mir-22-3p Inhibit Monosodium Urate-Induced Gouty Inflammation By Targeting Nlrp3

INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES(2021)

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摘要
Background MicroRNAs (miRNAs) have been shown to play a crucial role in inflammation regulation; however, their relationship with inflammation in acute gouty arthritis has not been fully elucidated. Herein, we conducted a study to explore the regulatory roles of miR-223-3p and miR-22-3p in gouty-associated inflammation.Methods In vitro and in vivo experiments were conducted to examine the molecular mechanisms of miRNA regulation in gouty inflammation. Dual-luciferase reporter assay was used to verify the direct target of miR-223-3p and miR-22-3p.Results We found that miR-223-3p and miR-22-3p interacted with the 3 ' untranslated region segment of NLRP3 (nucleotide-binding domain leucine-rich repeat [NLR] and pyrin domain containing receptor 3) and inhibited its expression. A decreased expression of miR-223-3p and miR-22-3p was observed in both mice air pouch synovium and phorbol myristrate acetate-treated THP-1 cells stimulated with monosodium urate (P < .05). Compared with the negative control group, NLRP3 expression at the transcript and protein level in miR-223-3p and miR-22-3p overexpression group significantly decreased after 6 hours of monosodium urate treatment in vivo and in vitro (P < .05). The results of the dual-luciferase reporter assay demonstrated that miR-223-3p and miR-22-3p directly targeted NLRP3.Conclusion The findings of the present study show that miR-223-3p and miR-22-3p can reduce the inflammatory effects of gout by inhibiting the expression of NLRP3.
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关键词
gouty inflammation, miR&#8208, 223&#8208, 3p, miR&#8208, 22&#8208, 3p, monosodium urate, NLRP3
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