微小RNA-146a通过抑制TRAF6减轻缺氧诱导后巨噬细胞炎症反应
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1.南京医科大学附属儿童医院;2.Guo hongli

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国家自然科学基金青年项目(81800530)


MicroRNA-146a Mitigates hypoxia-induced Inflammatory Responses in Macrophages by suppressing TRAF6
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National Natural Science Foundation of China (81800530)

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    摘要:

    [摘要] 目的 探讨微小RNA-146a在缺氧诱导后巨噬细胞中的作用。方法 通过建立体外巨噬细胞缺氧-复氧模型,检测缺氧诱导后巨噬细胞中微小RNA-146a/TRAF6的表达水平及炎症因子、活性氧自由基的变化,并通过在巨噬细胞中过表达或抑制微小RNA-146a,分析其对巨噬细胞炎症反应的作用。结果 我们发现缺氧诱导巨噬细胞中微小RNA-146a表达下降,同时,TRAF6以及炎症因子、氧自由基表达升高。过表达微小RNA-146a直接减少TRAF6的表达,从而减轻了巨噬细胞炎症反应及氧自由基的释放,然而,转染微小RNA-146a抑制剂增加TRAF6的蛋白水平,导致炎症因子表达增加。结论 上调微小RNA-146a的表达通过直接抑制TRAF6,从而减轻了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中巨噬细胞释放炎症因子及氧自由基导致的损伤。

    Abstract:

    [Abstract] Objective To explore the role of microRNA-146a (miR-146a) in hypoxia induced macrophages. Mehhod The expression of miR-146a/TRAF6, inflammatory factors and reactive oxygen species(ROS) in macrophages were determinated under hypoxia-reoxygenation model. Moreover, release of inflammatory factors and ROS were analyzed after mimic or inhibitor of miR-146a. Results We found that the miR-146a levels were obviously decreased in hypoxia induced macrophages, while the expression of TRAF6, inflammatory factors and ROS increased. Overexpression of miR-146a directly 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 inflammation 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 cytokines and ROS in macrophages

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  • 收稿日期:2024-08-08
  • 最后修改日期:2024-10-14
  • 录用日期:2024-12-04
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