Lipopolysaccharide Inhibits Alpha Epithelial Sodium Channel Expression via MiR-124-5p in Alveolar Type 2  Epithelial Cells

• Published in: BioMed research international 2020, Vol.2020, p.8150780-9
• Main Authors: Ding, Yan, Cui, Yong, Zhou, Zhiyu, Hou, Yapeng, Pang, Xining, Nie, Hongguang
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; Acute Lung Injury - metabolism; Alveolar Epithelial Cells - drug effects; Alveolar Epithelial Cells - metabolism; Alveoli; Amiloride; Amiloride - pharmacology; Animals; Chromosome 5; Culture Media, Conditioned; Epithelial cells; Epithelial Sodium Channel Blockers - pharmacology; Epithelial Sodium Channels - biosynthesis; Epithelial Sodium Channels - genetics; Epithelial Sodium Channels - metabolism; Fibroblasts; Genetic research; Ion Transport; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Lung diseases; Lungs; Male; Mesenchymal Stem Cells - drug effects; Mesenchymal Stem Cells - metabolism; Mesenchyme; Mice; MicroRNAs; MicroRNAs - metabolism; miRNA; Mitogens; Pathogens; Penicillin; Polymerase chain reaction; Protein expression; Proteins; Sodium; Stem cell transplantation; Stem cells
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2020/8150780

Mesenchymal stem cells (MSCs) have been a potential strategy in the pretreatment of pulmonary diseases, while the mechanisms of MSCs-conditioned medium (MSCs-CM) involved with microRNAs on the regulation of lung ion transport are seldom reported. We investigated the role of miR-124-5p in lipopolysaccharide-involved epithelial sodium channel (ENaC) dysfunction and explored the potential target of miR-124-5p. We observed the lower expression of miR-124-5p after the administration of MSCs-CM, and the overexpression or inhibition of miR-124-5p regulated epithelial sodium channel α-subunit (α-ENaC) expression at protein levels in mouse alveolar type 2 epithelial (AT2) cells. We confirmed that α-ENaC is one of the target genes of miR-124-5p through dual luciferase assay and Ussing chamber assay revealed that miR-124-5p inhibited amiloride-sensitive currents associated with ENaC activity in intact H441 monolayers. Our results demonstrate that miR-124-5p can decrease the expression and function of α-ENaC in alveolar epithelial cells by targeting the 3′-UTR. The involvement of MSCs-CM in lipopolysaccharide-induced acute lung injury cell model could be related to the downregulation of miR-124-5p on α-ENaC, which may provide a new target for the treatment of acute lung injury.