Epidermal stem cells participate in the repair of scalds via Nanog and Myc regulation

Epidermal stem cells (EpSCs) with high expression of regulatory factor Nanog can promote wound healing. The aim of the present study was to investigate the effectiveness and mechanism of epidermal stem cells (EpSCs) in healing scalds and the underlying molecular mechanism. Mouse EpSCs were isolated from skin tissues and cultured in vitro. First, the proliferative ability of EpSCs was determined via the upregulation and downregulation of Nanog expression levels in EpSCs using the MTS-assay. Second, a wound healing assay of the EpSCs with different Nanog expression levels was performed to investigate cell migratory capacities. Third, the protein expression levels of various proteins in EpSCs with Nanog overexpression or knockdown, were determined. Finally, the transfected EpSCs were applied to the rat scald model to observe their effect on scald healing. Subsequently, wound scores, re-epithelialization and capillary density were determined histologically. The results demonstrated that Nanog overexpression enhanced the proliferative ability of EpSCs via cellular (c)-Myc. Moreover, the LV-Nanog group of EpSCs with increased Nanog expression levels exhibited improved healing abilities in the wound healing test than control group. Using western blotting, it was demonstrated that EpSCs that were transfected with a Nanog-overexpression vector expressed high Nanog protein expression levels, whereas small interfering RNA-Nanog-transfected EpSCs exhibited low Nanog protein expression levels. Furthermore, c-Myc expression was synchronized with Nanog expression. It was also revealed that as the expression levels of c-Myc increased, p53 expression levels also increased. In the rat scald model, Nanog-overexpressing EpSCs enhanced wound closure and re-epithelialization. The EpSCs with Nanog knockdown exhibited the opposite effects. The present study therefore indicated that Nanog may have a positive effect on scald healing in rats, which supports its use in EpSC-based treatments against scalds. Furthermore, it was suggested that c-Myc potentially serves a key role in this process and that this process avoids cancerization by relying on the supervision of p53.