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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >MicroRNAs are dynamically regulated and play an important role in LPS-induced lung injury
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MicroRNAs are dynamically regulated and play an important role in LPS-induced lung injury

机译：MicroRNA被动态调节，并在LPS诱导的肺损伤中起重要作用

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摘要

Acute lung injury is characterized by an increase of inflammatory reaction and severe lung edema. Even if there have been great advances in the identification of genes and signaling pathways involved in acute lung injury, the fundamental mechanisms of initiation and propagation of acute lung injury have not been understood completely. A growing amount of evidence indicates that microRNAs (miRNAs) are involved in various human diseases. However, the expression profile and function of miRNAs in acute lung injury have not been investigated. Here, using real-time polymerase chain reaction analysis, we show that a collection of miRNAs is dynamically regulated in lipopolysaccharide (LPS)-induced mouse acute lung injury. Among them, miR-199a and miR-16 are the most significantly down-regulated miRNAs. To study the role of miR-199a and miR-16 in acute lung injury, an over-expression of miR-199a or miR-16 assay was performed in LPS-treated A549 cells, and then the expression of inflammatory factors was analyzed. Over-expression of miR-199a could not alter the expression level of interleukin (IL)-6 and tumor necrosis factor-alpha (TNFa), while up-regulation of miR-16 could significantly down-regulate IL-6 and TNFα expression level. Using bioinformatic analysis, we show that a 3' untranslational region (UTR) of IL-6 and TNFα contains the binding sites of miR-16. Accordingly, over-expression of miR-16 could significantly suppress the luciferase activity of reporter fusion with the binding sites of TNFα in its 3'UTR region, suggesting that miR- 16 played its role in LPS-induced lung inflammation by a direct manner. In this study, we show for the first time that miRNAs are dynamically regulated and play an important function in LPS-induced lung injury.
机译：急性肺损伤的特征是炎症反应增加和严重的肺水肿。即使在急性肺损伤涉及的基因和信号通路的鉴定方面取得了很大的进步，急性肺损伤的起始和传播的基本机制仍未完全了解。越来越多的证据表明，microRNA（miRNA）与多种人类疾病有关。但是，尚未研究miRNA在急性肺损伤中的表达特征和功能。在这里，使用实时聚合酶链反应分析，我们表明，miRNA的集合在脂多糖（LPS）诱导的小鼠急性肺损伤中被动态调节。其中，miR-199a和miR-16是最明显下调的miRNA。为了研究miR-199a和miR-16在急性肺损伤中的作用，在LPS处理的A549细胞中进行了miR-199a或miR-16的过表达，然后分析了炎症因子的表达。 miR-199a的过表达不能改变白介素（IL）-6和肿瘤坏死因子-α（TNFa）的表达水平，而miR-16的上调则可以显着下调IL-6和TNFα的表达水平。使用生物信息学分析，我们显示IL-6和TNFα的3'非翻译区（UTR）包含miR-16的结合位点。因此，miR-16的过表达可以显着抑制报告基因与3'UTR区域中TNFα结合位点融合的荧光素酶活性，表明miR-16通过直接方式在LPS诱导的肺部炎症中发挥作用。在这项研究中，我们首次证明了miRNA是动态调节的，并且在LPS诱导的肺损伤中起重要作用。

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