hUC‐MSCs exosomal miR‐451 alleviated acute lung injury by modulating macrophage M2 polarization via regulating MIF‐PI3K‐AKT signaling pathway

Abstract In the previous study, we have proved that exosomal miR‐451 from human umbilical cord mesenchymal stem cells (hUC‐MSCs) attenuated burn‐induced acute lung injury (ALI). However, the mechanism of exosomal miR‐451 in ALI remains unclear. Therefore, this study aimed to study the molecular mechanism of hUC‐MSCs‐derived exosomal miR‐451 on ALI by regulating macrophage polarization. Exosomes were isolated and identified by transmission electron microscope (TEM) and nanoparticle tracking analysis (NTA). The expression of miR‐451, macrophage migration inhibitory factor (MIF) and PI3K/AKT signaling pathway proteins were detected by qRT‐PCR and western blot. Flow cytometry was used to detect the CD80 and CD206 positive cells. Severe burn rat model was established and HE was used to detect the inflammatory cell infiltration and inflammatory injury. Dual luciferase reporter system was used to detect the regulation of miR‐451 to MIF. The contents of cytokines were detected by ELISA. The results showed that hUC‐MSCs exosomes promoted macrophage M1 to M2 polarization. Furthermore, hUC‐MSCs‐derived exosomal miR‐451 alleviated ALI development and promoted macrophage M1 to M2 polarization. Moreover, MIF was a direct target of miR‐451. Downregulation of MIF regulated by miR‐451 alleviated ALI development promoted macrophage M1 to M2 polarization. In addition, we found that MIF and hUC‐MSCs‐derived exosomal miR‐451 participated in ALI by regulating PI3K/AKT signaling pathway. In conclusion, we indicated that hUC‐MSCs‐derived exosomal miR‐451 alleviated ALI by modulating macrophage M2 polarization via regulating MIF‐PI3K‐AKT signaling pathway, which provided great scientific significance and clinical application value for the treatment of burn‐induced ALI.