Macrophage polarization is an important effector process in acute lung injury (ALI) induced by sepsis. MicroRNAs (miRNAs) have emerged as important players in regulating ALI process. Here, we showed that elevated microRNA-23a-3p (miR-23a-3p) promoted LPS-induced macrophage polarization and ALI in mice, while inhibition of miR-23a-3p led to reduced macrophage response and ameliorated ALI inflammation. Mechanically, miR-23a-3p regulated macrophage M1 polarization through targeting polo-like kinase 1 (PLK1). PLK1 was downregulated in LPS-treated macrophages and ALI mouse lung tissues. Knockdown of PLK1 increased macrophage M1 polarization through promoting STAT1/STAT3 activation, while overexpression of PLK1 reduced macrophage immune response. Collectively, our results reveal a key miRNA regulon that regulates macrophage polarization for LPS-induced immune response.

中文翻译：

---

MicroRNA-23a-3p通过调节PLK1/STAT1/STAT3信号促进巨噬细胞M1极化并加重脂多糖诱导的急性肺损伤

巨噬细胞极化是脓毒症引起的急性肺损伤（ALI）的重要效应过程。MicroRNA (miRNA) 已成为调节 ALI 过程的重要参与者。在这里，我们发现，升高的 microRNA-23a-3p (miR-23a-3p) 会促进 LPS 诱导的小鼠巨噬细胞极化和 ALI，而抑制 miR-23a-3p 会导致巨噬细胞反应减少并改善 ALI 炎症。从机械角度来说，miR-23a-3p 通过靶向 polo 样激酶 1 (PLK1) 来调节巨噬细胞 M1 极化。PLK1 在 LPS 处理的巨噬细胞和 ALI 小鼠肺组织中下调。PLK1 的敲低通过促进 STAT1/STAT3 激活来增加巨噬细胞 M1 极化，而 PLK1 的过度表达会降低巨噬细胞的免疫反应。总的来说，我们的结果揭示了一个关键的 miRNA 调节子，它调节 LPS 诱导的免疫反应的巨噬细胞极化。