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

Abstract

Background

Adipose 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.

Methods

The 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.

Results

35 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.

Conclusions

AMSC-derived exosomal miR-223–3p may accelerate wound healing by targeting MAPK10.