Exosomal miR-451 from human umbilical cord mesenchymal stem cells attenuates burn-induced acute lung injury.

Abstract

The aim of this study was to investigate the molecular mechanism of human umbilical cord mesenchymal stem cells (MSCs)-derived exosomes (hUCMSC-Exos) in regulating burn-induced acute lung injury (ALI). In this study, we initially isolated exosomes from hUCMSCs and identified them by transmission electron microscopy. The expression of the protein markers CD9 and CD63 in the exosomes was determined by western blot analysis. The expression of miR-451 in the hUCMSC-Exos was determined by qRT-PCR. The levels of TNF-α, IL-1β, and IL-6 in lung tissues and serum as well as the levels of malondialdehyde, myeloperoxidase, superoxide dismutase in lung tissues were detected by ELISA. Hematoxylin-eosin stain was used to observe the morphological changes of lung tissues after burn. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assays were performed to detect apoptosis in lung tissues after burn. The expression of proteins related to the Toll-like receptor 4 (TLR4)/NF-κB signaling pathway in lung tissues after burn was analyzed by western blotting. Our results showed that hUCMSC-Exos successfully decreased TNF-α, IL-1β, and IL-6 levels in rats after burn, and this reduction was reversed when the miR-451 expression in the hUCMSC-Exo group was inhibited. HUCMSC-Exo-derived miR-451 improves ALI via the TLR4/NF-κB pathway. We demonstrated that exosomes derived from hUCMSCs mediate miR-451 to attenuate burn-induced ALI.