Potential role of Wnt signaling pathway in epidermal cell dedifferentiation under traumatic microenvironment / 中华创伤杂志

ABSTRACT

Objective To investigate the inductive role of traumatic microenvironment in dedifferentiation of epidermal cells and explore the potential role of Wnt signaling pathway in this biological process. Methods The sheets of human foreskin were digested overnight after removal of adipose tissue, and then the epidermis was separated from the dermis. The separated epidermis sheets were repeatedly adhered to type Ⅳ collagen and flushed to remove the epidermal stem cells. The obtained epidermis sheets were transplanted onto the full-thickness skin wounds on the back of BALB/c nude mice, five days after which the cell lineage was evaluated by immunohistochemistry and the expressions of Wnts and downstream components in the grafted epidermal sheets examined by RT-PCR and Western blot. Results The cells in the basal layer of full-thickness epidermal sheets were positive for CK19 and β1 integrin and negative for CK10. While the cells in uhrathin epidermal sheets treated with type Ⅳ collagen were fully positive for CK10. Five days after transplantation of the ultrathin epidermal sheets, cells negative for CK10 but positive for CK19 and β1 integrin emerged at the wound-neighboring side of the skin grafts. At the same time, the expressions of Wnt-10b, Wnt-4 and Wnt-7a mRNA were increased by about 3.1-fold, 2.2-fold and 1.4-fold independently after transplantation. Furthermore, the expressions of β-catenin and β-catenin target genes (cyclin D1 and c-myc) were elevated by about 3-fold, 1.5-fold and 2-fold respectively in the grafted epidermal sheets (P < 0.01). Conclusion Traumatic microenvironment can induce epidermal cell dedifferentiation, when the Wnt/β -catenin signaling pathway may play an important role.