Co-culture with human fetal epidermal keratinocytes promotes proliferation and migration of human fetal and adult dermal fibroblasts

The repair strategy for the healing of skin wounds in fetuses differs from that in adults. Proliferation and migration of dermal fibroblasts are the main mechanisms associated with skin wound healing, as well as the complex interactions between epidermal keratinocytes (KCs) and dermal fibroblasts. In order to investigate the effects of fetal skin epidermal KCs on fetal and adult human dermal fibroblasts, KCs and fibroblasts were isolated from the skin tissue of mid-gestational human fetuses and adults, and co-cultured using a Transwell (R) system. When fetal mid-gestational KCs were co-cultured with either fetal or adult dermal fibroblasts, the proliferative and migratory potential of the fibroblasts was significantly enhanced. Furthermore, these phenotypic changes were concomitant with the upregulation of numerous proteins including mouse double minute 2 homolog, cyclin B1, phospho-cyclin-dependent kinase 1, phospho-extracellular signal-regulated kinase, and phospho-AKT, along with C-X-C chemokine receptor 4, phospho-p38 mitogen activated protein kinase, matrix metalloproteinase (MMP)-2 and MMP-9. Notably, no significant differences were observed between fetal and adult dermal fibroblasts in their responses to fetal mid-gestational epidermal KCs, indicating that the cells from these two developmental stages respond in a similar manner to co-culture with KCs.