Exosomal miR-135a derived from human amnion mesenchymal stem cells promotes cutaneous wound healing in rats and fibroblast migration by directly inhibiting LATS2 expression

BACKGROUND: Wound healing is a complex pathophysiological process that involves a variety of cells and cytokines. In this study, we found that local injection of human amnion mesenchymal stem cells into wounds in rats could promote wound healing. Therefore, we hypothesized that the exosomes of human amnion mesenchymal stem cells contain substances that regulate the migration of epidermal cells. It has been reported that miR-135a is involved in cell migration and transformation. However, there have been no reports of its function in skin wound healing. METHODS: To test this hypothesis, we injected exosomes overexpressing miR-135a directly into the wound margin. In addition, we tested the migration of BJ cells with overexpression or knockdown of miR-135a in vitro. Additionally, Western blot analysis was used to detect the expression of fibroblast migration-associated proteins after treatment with miR-135a overexpression or knockdown. RESULTS: MiR-135a significantly promoted wound healing compared to the control treatment. Western blot analysis showed a significant downregulation of LATS2 after overexpression of miR-135a. In addition, knockdown of miR-135a effectively attenuated the promoting effect of exosomes on cell migration. CONCLUSIONS: Our results indicated that miR-135a promotes wound healing, which may be mediated by downregulating LATS2 levels to increase cell migration. This study provides a rationale for the therapeutic effect on wound healing of miR-135a in exosomes derived from human amnion mesenchymal stem cells.