miR-146a通过抑制TRAF6减轻缺氧诱导的巨噬细胞炎症反应
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1.南京医科大学附属儿童医院药学部 ;2.烧伤整形科,江苏 南京 210008

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R364

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国家自然科学基金(81800530)


miR-146a mitigates hypoxia-induced inflammatory responses in macrophages by suppressing TRAF6
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1.Department of Pharmacy ;2.Department of Burns and Plastic Surgery,Children’s Hospital of Nanjing Medical University,Nanjing 210008 ,China

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    摘要:

    目的:探讨miR-146a在缺氧诱导巨噬细胞炎症反应中的作用。方法:建立体外巨噬细胞缺氧-复氧模型,检测缺氧诱导巨噬细胞中miR-146a/肿瘤坏死因子受体相关因子6(tumor necrosis factor receptor-associated factor 6,TRAF6)的表达水平及炎症因子、活性氧的变化,并在巨噬细胞中过表达或抑制miR-146a,分析其对巨噬细胞炎症反应的作用。结果:缺氧诱导巨噬细胞中miR-146a表达下降,同时,TRAF6以及炎症因子、活性氧表达升高。过表达miR-146a通过直接靶向结合TRAF6减少 TRAF6的表达,从而减轻巨噬细胞炎症因子及活性氧的释放,然而,转染miR-146a抑制剂增加TRAF6的蛋白水平,增强炎症反应。结论:上调miR-146a的表达可直接抑制TRAF6,减轻缺氧诱导巨噬细胞的炎症反应。新的针对miR-146a治疗策略可能有利于减轻缺血再灌注时巨噬细胞释放的炎症因子及活性氧导致的损伤。

    Abstract:

    Objective:To explore the role of microRNA-146a(miR-146a)in hypoxia induced inflammatory responses in macrophages. Methods:The expression of miR-146a/tumor necrosis factor receptor-associated factor 6(TRAF6),inflammatory factors and reactive oxygen species(ROS)in macrophages were determined under hypoxia-reoxygenation model. Moreover,release of inflammatory factors and ROS were analyzed after mimic or inhibitor of miR-146a. Results:The miR-146a expression level was obviously decreased in hypoxia induced macrophages,while the expression of TRAF6,inflammatory factors and ROS increased. Overexpression of miR -146a directly targeted and decreased TRAF6 expression and reduced the release of inflammatory factors and ROS,however,transfection with miR-146a inhibitor increased the levels of TRAF6 and promoted inflammatory response. Conclusion: Overexpression of miR -146a attenuates the inflammation response in hypoxia induced macrophages by directly targeting the TRAF6 gene. New treatment strategies targeting miR -146a may help reduce ischemia-reperfusion injury caused by inflammatory factors and ROS in macrophages.

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蒋承烨,倪明明,孙尧,高庆文,孔亮亮,季易,郭宏丽. miR-146a通过抑制TRAF6减轻缺氧诱导的巨噬细胞炎症反应[J].南京医科大学学报(自然科学版),2024,(12):1657-1661,1689

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  • 收稿日期:2024-08-08
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  • 在线发布日期: 2024-12-16
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