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Up-regulation of microRNA-335-5p reduces inflammation via negative regulation of the TPX2-mediated AKT/GSK3β signaling pathway in a chronic rhinosinusitis mouse model
Cellular Signalling ( IF 4.4 ) Pub Date : 2020-03-07 , DOI: 10.1016/j.cellsig.2020.109596
Xiao Gu 1 , Xiaocui Yao 2 , Dengtao Liu 2
Affiliation  

Chronic rhinosinusitis (CRS) is featured with chronic symptoms of inflammation or infection in the nasal and sinus tissues. MicroRNAs (miRNAs/miRs), such as dysregulated expression of miR-125b and miR-26a, has been previously demonstrated to be related to CRS. The present study is intended to define the role of miR-335-5p in inflammation and the related mechanism in a mouse model of CRS. The differentially expressed genes associated with CRS were screened by microarray analysis. The targeting relationship between miR-335-5p and TPX2 was analyzed by target prediction program and dual luciferase reporter gene assay. The mouse model of CRS was established, and mice were introduced with miR-335-5p mimics, miR-335-5p inhibitors, or siRNA against TPX2 to explore the regulatory functions of miR-335-5p. The regulatory effect of miR-335-5p on inflammation with the involvement of the AKT signaling pathway was also analyzed with the expression of inflammatory cytokines and AKT signaling pathway-related factors measured. It was indicated that miR-335-5p regulated the TPX2 gene-mediated AKT signaling pathway. TPX2 was identified as a target gene of miR-335-5p, and miR-335-5p elevation inhibited the activation of the AKT signaling pathway. In mice with CRS, up-regulation of miR-335-5p or silence of TPX2 inhibited the inflammation, as evidenced by decreased levels of TNF-α, IL-6 and IL-8, and higher levels of GSK3β and IL-10. Collectively, miR-335-5p inhibits the activation of AKT signaling pathway by negatively mediating TPX2, which may confer anti-inflammatory protection in CRS.



中文翻译:

microRNA-335-5p 的上调通过负调节 TPX2 介导的 AKT/GSK3β 信号通路在慢性鼻鼻窦炎小鼠模型中减少炎症

慢性鼻窦炎 (CRS) 的特征是鼻和鼻窦组织的炎症或感染的慢性症状。MicroRNAs (miRNAs/miRs),例如 miR-125b 和 miR-26a 的失调表达,先前已被证明与 CRS 相关。本研究旨在确定 miR-335-5p 在炎症中的作用以及 CRS 小鼠模型中的相关机制。通过微阵列分析筛选与CRS相关的差异表达基因。通过靶标预测程序和双荧光素酶报告基因检测分析miR-335-5p与TPX2的靶向关系。建立CRS小鼠模型,将miR-335-5p模拟物、miR-335-5p抑制剂或针对TPX2的siRNA导入小鼠,探索miR-335-5p的调控功能。还通过测量炎症细胞因子的表达和测量的 AKT 信号通路相关因子来分析 miR-335-5p 对 AKT 信号通路参与的炎症的调节作用。表明miR-335-5p调控了TPX2基因介导的AKT信号通路。TPX2被确定为miR-335-5p的靶基因,miR-335-5p的升高抑制了AKT信号通路的激活。在患有 CRS 的小鼠中,miR-335-5p 的上调或 TPX2 的沉默抑制了炎症,这可以通过降低 TNF-α、IL-6 和 IL-8 的水平以及更高水平的 GSK3β 和 IL-10 来证明。总的来说,miR-335-5p 通过负介导 TPX2 抑制 AKT 信号通路的激活,这可能赋予 CRS 抗炎保护。

更新日期:2020-03-09
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