Popis: |
Using a nude mouse grafting model, we have demonstrated that normal-haired skin is regenerated in a graft containing hair buds and dissociated dermis. Altering the dermal component leads to changes typical of the human nevus sebaceus of Jadassohn (NSJ). The murine lesion is characterized by sebaceous gland hyperplasia, abortive hair follicles, and epidermal hyperplasia. The development of the NSJ-like lesion is independent of the epidermal component but dependent on a specific dermal fibroblast combination, namely, a hair-inductive follicular papilla fibroblast cell line plus BALB/c 3T3 fibroblasts. Non-hair-inductive follicular papilla cell lines in combination with BALB/c 3T3 fibroblasts are unable to induce the NSJ-like structure, indicating that hair-inductive signals play a central role in its pathogenesis. BALB/c 3T3 fibroblasts in combination with total cells from dissociated neonatal dermis produce abortive hair follicles, but the sebaceous gland hyperplasia is suppressed, suggesting the presence of suppressive endogenous dermal factors. The data suggest that (a) pilosebaceous induction is a multistep process and (b) the pathogenesis of NSJ involves perturbation of a complex array of inductive mesenchymal (dermal) signals. This paper describes the first animal model of NSJ and provides evidence that development of the human lesion could depend entirely on aberrant dermal cells. |