Mesenchymal stem cells (MSCs) have been widely documented for their potential role in the treatment of various clinical disorders, including acute lung injury (ALI). ALI represents a clinical syndrome associated with histopathological diffuse alveolar damage. Recent evidence has demonstrated that exosomes derived from MSCs may serve as a reservoir of anti-apoptotic microRNAs (miRs) conferring protection from certain diseases. Hence, the current study was performed with the aim of investigating whether MSCs-exosomal miR-30b-3p could confer protection against ALI. A bioinformatic analysis and a dual luciferase assay were initially performed to verify that SAA3 was highly-expressed in ALI which was confirmed to be a target gene of miR-30b-3p. Next, the lipopolysaccharide (LPS)-treated type II alveolar epithelial cells (AECs) (MLE-12) were transfected with mimics or inhibitors of miR-30b-3p, or sh-SAA3. It was revealed that LPS induced AEC apoptosis, which could be inhibited by overexpressing miR-30b-3p by down-regulating the expression of SAA3. After co-culture of PKH26-labeled exosomes with MLE-12 cells, we found that the number of PKH26-labeled exosomes endocytosed by MLE-12 cells gradually increased. Furthermore, the LPS-treated MLE-12 cells co-cultured with MSC-exosomes overexpressing miR-30b-3p exhibited increased miR-30b-3p, decreased SAA3 level, as well as increased cell proliferation, accompanied by diminished cell apoptosis in LPS-treated MLE-12 cells. Finally, the protective effect of MSCs-exosomal miR-30b-3p on the AECs in vivo was investigated in an ALI mouse model with tail vein injection of MSC-exosomes with elevated miR-30b-3p, showing that overexpression of miR-30b-3p in MSC-exosomes conferred protective effects against ALI. Taken together, these findings highlighted the potential of MSC-exosomes overexpressing miR-30b-3p in preventing ALI. The exosomes derived from MSCs hold potential as future therapeutic strategies in the treatment of ALI.
Keywords: Acute lung injury; Alveolar epithelial cells; Exosome; Mesenchymal stem cells; Serum amyloid A3; microRNA-30b-3p.
Copyright © 2019. Published by Elsevier Inc.