MicroRNA-23a-3p promotes macrophage M1 polarization and aggravates lipopolysaccharide-induced acute lung injury by regulating PLK1/STAT1/STAT3 signalling

IF 1.8 4区 医学 Q3 PATHOLOGY International Journal of Experimental Pathology Pub Date : 2022-06-23 DOI:10.1111/iep.12445
Tao Jiang, Li Sun, Jun Zhu, Ning Li, Haibo Gu, Ying Zhang, Miaomiao Li, Jiayao Xu
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引用次数: 4

Abstract

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.

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MicroRNA-23a-3p通过调节PLK1/STAT1/STAT3信号传导促进巨噬细胞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诱导急性肺损伤(ALI)的一个重要效应过程。微小RNA(miRNA)已成为调节ALI过程的重要参与者。在这里,我们发现,升高的微小RNA-23a-3p(miR-23a-3ps)促进了LPS诱导的小鼠巨噬细胞极化和ALI,而抑制miR-23a-3c导致巨噬细胞反应减少并改善了ALI炎症。在机制上,miR-23a-3p通过靶向polo-like激酶1(PLK1)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。敲低PLK1通过促进STAT1/STAT3活化增加巨噬细胞M1极化,而过表达PLK1降低巨噬细胞免疫反应。总之,我们的研究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。
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来源期刊
CiteScore
4.50
自引率
3.30%
发文量
35
审稿时长
>12 weeks
期刊介绍: Experimental Pathology encompasses the use of multidisciplinary scientific techniques to investigate the pathogenesis and progression of pathologic processes. The International Journal of Experimental Pathology - IJEP - publishes papers which afford new and imaginative insights into the basic mechanisms underlying human disease, including in vitro work, animal models, and clinical research. Aiming to report on work that addresses the common theme of mechanism at a cellular and molecular level, IJEP publishes both original experimental investigations and review articles. Recent themes for review series have covered topics as diverse as "Viruses and Cancer", "Granulomatous Diseases", "Stem cells" and "Cardiovascular Pathology".
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