miR-17 调控脂多糖诱导的急性肺损伤中肺组织 FoxA1 的表达
The microRNA miR-17 regulates lung FoxA1 expression during lipopolysaccharide-induced acute lung injury.
机构信息
Cardiothoracic Surgery of the First Affiliated Hospital, Hunan University of Traditional Chinese Medicine, Changsha, Hunan 41007, China.
University of South China, College of Life Science, Department of Biochemistry and Molecular Biology, Hengyang, Hunan 421001, China.
出版信息
Biochem Biophys Res Commun. 2014 Feb 28;445(1):48-53. doi: 10.1016/j.bbrc.2014.01.108. Epub 2014 Jan 31.
Acute lung injury (ALI) is a severe pulmonary disease that causes a high number of fatalities worldwide. Studies have shown that FoxA1 expression is upregulated during ALI and may play an important role in ALI by promoting the apoptosis of alveolar type II epithelial cells. However, the mechanism of FoxA1 overexpression in ALI is unclear. In this study, an in vivo murine model of ALI and alveolar type II epithelial cells injury was induced using lipopolysaccharide (LPS). LPS upregulated FoxA1 in the lung tissue of the in vivo ALI model and in LPS-challenged type II epithelial cells. In contrast, miR-17 was significantly downregulated in these models. After miR-17 antagomir injection, the expression of FoxA1 was significantly increased in ALI mice. MiR-17 mimics could significantly inhibit FoxA1 mRNA and protein expression, whereas the miR-17 inhibitor could significantly increase FoxA1 mRNA and protein expression in LPS-induced type II epithelial cells. Thus, our results suggest that the downregulation of miR-17 expression could lead to FoxA1 overexpression in ALI.
急性肺损伤（ALI）是一种严重的肺部疾病，在全球范围内导致大量死亡。研究表明，FoxA1 的表达在 ALI 期间上调，可能通过促进肺泡 II 型上皮细胞凋亡在 ALI 中发挥重要作用。然而，FoxA1 在 ALI 中的过度表达的机制尚不清楚。在这项研究中，使用脂多糖（LPS）诱导体内 ALI 和肺泡 II 型上皮细胞损伤的小鼠模型。LPS 上调体内 ALI 模型和 LPS 刺激的 II 型上皮细胞中的 FoxA1。相比之下，miR-17 在这些模型中显著下调。在 ALI 小鼠中注射 miR-17 拮抗剂后，FoxA1 的表达明显增加。miR-17 模拟物可显著抑制 FoxA1 mRNA 和蛋白表达，而 miR-17 抑制剂可显著增加 LPS 诱导的 II 型上皮细胞中 FoxA1 mRNA 和蛋白表达。因此，我们的结果表明，miR-17 表达的下调可能导致 ALI 中 FoxA1 的过度表达。
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