MiR-199a-3p in mouse bone marrow mesenchymal stem cell exosomes increases epithelial sodium channel expression in lung injury

Fundam Clin Pharmacol. 2022 Dec;36(6):1011-1019. doi: 10.1111/fcp.12807. Epub 2022 Jun 10.

Abstract

Acute lung injury (ALI) causes significant morbidity and mortality in critically ill patients, which often presents with extensive accumulation of activated inflammatory cells and diffused alveolar damage accompanied by oxidative stress. Exosomes are nanovesicles, which have notable anti-inflammatory and repair properties, thus alleviating the symptoms of ALI. Epithelial sodium channel (ENaC) is essential for the transepithelial absorption of Na+ and fluid from alveolar spaces. We studied the effects of bone marrow mesenchymal stem cell exosomes (BMSC-exo) on the apoptosis and protein expression of ENaC in primary mouse alveolar epithelial type 2 cells (AT 2 cells). Moreover, the change of miR-199a-3p in AT 2 cells was detected by qRT-PCR, and we studied the regulation of miR-199a-3p on ENaC protein expression. Our results demonstrated that BMSC-exo could not only improve viability and reduce apoptosis in AT 2 cells, but also enhance the expression of ENaC protein and miR-199a-3p. Meanwhile, the upregulation of miR-199a-3p resulted in increased expression of ENaC protein. In summary, the BMSC-exo could participate in the regulation of ENaC through miR-199a-3p originated from BMSC-exo, thereby providing a new pharmacological tool for the treatment of ALI.

Keywords: acute lung injury; bone marrow mesenchymal stem cells; epithelial sodium channel; exosomes; miR-199a-3p.

MeSH terms

  • Acute Lung Injury* / metabolism
  • Animals
  • Epithelial Sodium Channels* / genetics
  • Epithelial Sodium Channels* / metabolism
  • Exosomes* / metabolism
  • Mesenchymal Stem Cells* / metabolism
  • Mice
  • MicroRNAs* / genetics

Substances

  • Epithelial Sodium Channels
  • MicroRNAs
  • Mirn199 microRNA, mouse