MiR‐223‐3p and miR‐22‐3p inhibit monosodium urate‐induced gouty inflammation by targeting NLRP3

• Published in: International journal of rheumatic diseases Vol. 24; no. 4; pp. 599 - 607
• Main Authors: Wang, Xiang, Chi, Jingwei, Dong, Bingzi, Xu, Lili, Zhou, Yue, Huang, Yajing, Sun, Shengnan, Wei, Fanxiang, Liu, Yuzhao, Liu, Chuanfeng, Che, Kui, Lv, Wenshan, Chen, Ying, Wang, Yangang
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.04.2021
• Subjects: 3' Untranslated Regions; Acetic acid; Animals; Arthritis; Arthritis, Gouty - chemically induced; Arthritis, Gouty - immunology; Arthritis, Gouty - metabolism; Arthritis, Gouty - prevention & control; Binding Sites; Disease Models, Animal; Down-Regulation; Gout; gouty inflammation; Humans; Inflammasomes - genetics; Inflammasomes - metabolism; Inflammation; Inflammation - chemically induced; Inflammation - immunology; Inflammation - metabolism; Inflammation - prevention & control; Leucine; Male; Mice; Mice, Inbred BALB C; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; miR‐223‐3p; miR‐22‐3p; Molecular modelling; monosodium urate; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3; Pyrin protein; Signal Transduction; Synovium; THP-1 Cells; Transcription; Uric Acid; NLRP3; gouty inflammation; miR-223-3p; monosodium urate; miR-22-3p
• ISSN: 1756-1841; 1756-185X
• DOI: 10.1111/1756-185X.14089

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.