MiR-223–3p overexpressed adipose mesenchymal stem cell-derived exosomes promote wound healing via targeting MAPK10

Abstract

BackgroundAdipose mesenchymal stem cell (AMSC)-derived exosomes are promising novel factors for wound repair and regeneration. This study aimed to explore the potential roles and underlying mechanisms of specific miRNA in wound healing using AMSC-derived exosomes as carriers. MethodsThe expression profiles of GSE197840 were downloaded to screen for differentially expressed miRNAs (DEmiRNAs), and the corresponding genes of the identified miRNAs were predicted. Next, miRNA-mRNA co-expression networks were constructed and the genes in these networks were subjected to functional analysis. miR-223–3p overexpressed AMSCs were then established to isolate exosomes, and the effects of AMSC-derived exosomes carrying miR-223–3p on wound healing and the related potential mechanisms were further investigated in vivo. Results35 DEmiRNAs were identified and a co-expression network containing 22 miRNAs and 91 target genes was constructed. Based on the network, miR-223–3p was the hub node and the genes were significantly enriched in 15 GO terms of biological processes and 14 KEGG pathways, including cAMP, PI3K-Akt, cGMP-PKG, neurotrophin signaling pathway, and dopaminergic synapse. Then, miR-223–3p overexpressed AMSCs-derived exosomes were successfully extracted, and miR-223–3p was found to directly bind with MAPK10. In vivo experiments validated that AMSCs-derived exosomal miR-223–3p could promote wound healing, and up-regulated α-SMA, CD31, COL1A1, COL2A1, COL3A1, and down-regulated MAPK10, TNF-α, IL-β, and IL-6. ConclusionsAMSC-derived exosomal miR-223–3p may accelerate wound healing by targeting MAPK10.