Department of Rheumatology and Immunology, Zhoushan Hospital of Zhejiang Province, Zhoushan 316021, Zhejiang, China.
Cell Cycle. 2022 Apr;21(8):805-819. doi: 10.1080/15384101.2022.2031678. Epub 2022 Mar 3.
Gouty arthritis (GA) is caused by monosodium urate (MSU) crystal accumulation in the joints. MSU-mediated inflammation is an important inducing factor in gouty arthritis (GA). Recent studies have demonstrated that microRNAs can influence GA progression. Herein, the role and mechanism of miRNA-142-3p in GA were explored. To establish the and GA models, MSU was used to induce inflammatory response in human monocyte cell line THP-1 and male C57BL/6 mice. Protein levels, gene expression and proinflammatory cytokine secretion were respectively tested by Western blotting, RT-qPCR, and enzyme-linked immunosorbent assay (ELISA). Pathological changes in sagittal sections of ankle tissues were exhibited by hematoxylin-eosin (HE) staining. Binding relationship between miRNA-142-3p and zinc finger E-box binding homeobox 2 (ZEB2) was predicted and confirmed by bioinformatics analysis and luciferase reporter assay. In this study, MSU induced inflammatory response and upregulated miRNA-142-3p in THP-1 cells. Functionally, miRNA-142-3p knockdown inhibited inflammatory response in MSU-stimulated THP-1 cells and alleviated pathological symptoms of GA mice. Mechanically, miRNA-142-3p targeted ZEB2 in THP-1 cells. ZEB2 expression was elevated in MSU-administrated THP-1 cells and GA mice. ZEB2 downregulation reserved the inhibitory effect of miRNA-142-3p deficiency on inflammatory response in MSU-treated THP-1 cells. In addition, miRNA-142-3p activated NF-κB signaling by binding with ZEB2 in THP-1 cells upon MSU stimulation. Overall, miRNA-142-3p facilitates inflammatory response by targeting ZEB2 and activating NF-κB signaling in GA.
痛风性关节炎（GA）是由单钠尿酸盐（MSU）晶体在关节中积累引起的。MSU 介导的炎症是痛风性关节炎（GA）的重要诱导因素。最近的研究表明，microRNAs 可以影响 GA 的进展。本文探讨了 microRNA-142-3p 在 GA 中的作用和机制。为了建立 和 GA 模型，用 MSU 诱导人单核细胞系 THP-1 和雄性 C57BL/6 小鼠的炎症反应。通过 Western blot、RT-qPCR 和酶联免疫吸附试验（ELISA）分别检测蛋白水平、基因表达和促炎细胞因子分泌。通过苏木精-伊红（HE）染色显示踝关节组织矢状切片的病理变化。通过生物信息学分析和荧光素酶报告基因实验预测并证实了 microRNA-142-3p 与锌指 E 盒结合同源盒 2（ZEB2）之间的结合关系。在这项研究中，MSU 诱导了 THP-1 细胞的炎症反应并上调了 microRNA-142-3p。功能上，microRNA-142-3p 敲低抑制了 MSU 刺激的 THP-1 细胞中的炎症反应，并缓解了 GA 小鼠的病理症状。机制上，microRNA-142-3p 在 THP-1 细胞中靶向 ZEB2。MSU 处理的 THP-1 细胞和 GA 小鼠中 ZEB2 的表达升高。ZEB2 下调保留了 microRNA-142-3p 缺陷对 MSU 处理的 THP-1 细胞中炎症反应的抑制作用。此外，microRNA-142-3p 在 MSU 刺激的 THP-1 细胞中通过与 ZEB2 结合激活 NF-κB 信号通路。总之，microRNA-142-3p 通过靶向 ZEB2 并激活 NF-κB 信号通路促进 GA 中的炎症反应。
