Exosomal miR-451a Derived from Bone Marrow Mesenchymal Stem Cells Inhibits Macrophage M1 Polarization Through the MIF/CD74 Signaling Pathway to Alleviate Acute Lung Injury.

Abstract

BACKGROUND: Macrophage polarization is widely involved in the progression of acute lung injury (ALI). Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) have been reported to participate ininflammatory diseases by regulating macrophage polarization. This study aimed to investigate the role of BMSC-Exos in ALI through the regulation of macrophage polarization. METHODS: LPS-induced ALI mouse models and RAW264.7 cell injury models were established. Lung injury was assessed through HE staining and assessment of bronchoalveolar lavage fluid (BALF) protein contents, the lung wet/dry weight ratios, and lung myeloperoxidase (MPO) activities. The expression of protein was detected via Western blotting and immunofluorescence. Exosomes were characterized using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). RESULTS: BMSC-Exos significantly alleviated pathological lung injury in ALI mice; reduced the lung wet/dry weight ratio, BALF protein content, MPO activity. BMSC-Exos inhibited LPS-induced macrophage M1 polarization and reduced proinflammatory cytokine expression. The molecular mechanism revealed that the BMSC-Exos delivered miR-451a to the macrophages and that inhibition of miR-451a expression attenuated the suppressive effect of the BMSC-Exos on M1 polarization. Furthermore, miR-451a targeted MIF to inhibit the MIF/CD74 signaling pathway. CONCLUSION: BMSC-Exos inhibit MIF/CD74 signaling by delivering miR-451a, thereby suppressing LPS-induced M1 macrophage polarization and alleviating ALI.