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

Int J Exp Pathol. 2022 Oct;103(5):198-207. doi: 10.1111/iep.12445. Epub 2022 Jun 23.

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.

Keywords: PLK1; acute lung injury; macrophage; microRNA-23.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury* / chemically induced
  • Acute Lung Injury* / genetics
  • Animals
  • Cell Cycle Proteins
  • Lipopolysaccharides / adverse effects
  • Macrophages
  • Mice
  • MicroRNAs* / genetics
  • Polo-Like Kinase 1
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins
  • STAT1 Transcription Factor / genetics

Substances

  • Cell Cycle Proteins
  • Lipopolysaccharides
  • MicroRNAs
  • Mirn23b microRNA, mouse
  • Proto-Oncogene Proteins
  • STAT1 Transcription Factor
  • Stat1 protein, mouse
  • Protein Serine-Threonine Kinases