Exosomal miR-127-5p from BMSCs alleviated sepsis-related acute lung injury by inhibiting neutrophil extracellular trap formation

Abstract

Neutrophil extracellular traps (NETs) play an important role in sepsis-related acute lung injury (ALI). Bone marrow mesenchymal stem cells (BMSCs)-derived exosomes and miRNA are becoming promising agents for the treatment of ALI. The current study aimed to elucidate the mechanism by BMSCs-derived exosomes carrying miR-127-5p inhibiting to the formation of NETs in sepsis-related ALI. We successfully isolated exosomes from BMSCs and confirmed that miR-127-5p was enriched in the exosomes. ALI mice treated with BMSCs-derived exosomes histologically improved, and the release of NETs and inflammatory factors in lung tissue and peripheral blood of mice also decreased compared with LPS group, while the protective effect of exosomes was attenuated after the knockdown of miR-127-5p. Using dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay, we identified CD64 as a direct target of miR-127-5p. Meanwhile, BMSCs-derived exosomes can synergize with anti-CD64 mab in ALI mice to reduce tissue damage, inhibit the release of inflammatory factors and NETs formation. The synergistic effect of exosomes was attenuated when miR-127-5p was down-regulated. These findings suggest that exosomal miR-127-5p derived from BMSCs is a potential therapeutic agent for treatment of sepsis-induced ALI through reducing NETs formation by targeting CD64.

Keywords: Bone marrow mesenchymal stem cells; CD64; Exosomes; Neutrophil extracellular traps; Sepsis-related acute lung injury.