Exosomal miR-223 promotes ARDS by targeting insulin-like growth factor 1 receptor: A cell communication study.

Abstract

Background: Acute respiratory distress syndrome (ARDS) is a respiratory failure syndrome characterized by hypoxemia and changes in the respiratory system. ARDS is the most common cause of death in COVID-19 deaths was ARDS. In this study, we explored the role of miR-223 in exosomes in ARDS.

Methods: Exosomes were purified from the supernatants of macrophages. qPCR was used to detect relative mRNA levels. A luciferase reporter assay was performed to verify the miRNA target genes. Western blotting was used to detect the activation of inflammatory pathways. Flow cytometry was performed to assess apoptosis. An LPS-induced ARDS mouse model was used to assess the function of miR-223 in ARDS.

Results: Exosomes secreted by macrophages promoted apoptosis in A549 cells. Macrophages and exosomes contain high levels of miR-223. Exogenous miR-223 can decrease the expression of insulin-like growth factor 1 receptor (IGF-1R) in A549 and promote the apoptosis of A549.Transfection of anti-miR223 antisense nucleotides effectively reduced the level of miR-223 in macrophages and exosomes and eliminated the pro-apoptotic effect of A549. In vivo, LPS stimulation increased inflammatory cell infiltration in the lungs of mice, whereas knockdown of miR-223 in mice resulted in significantly reduced eosinophil infiltration.

Conclusions: Macrophages can secrete exosomes containing miR-223 and promote apoptosis by targeting the IGF-1R/Akt/mTOR signaling pathway in A549 cells and mouse models, suggesting that miR-223 is a potential target for treating COVID-19 induced ARDS.