PPARδ Activation Promotes Stratum Corneum Formation and Epidermal Permeability Barrier Development during Late Gestation

The goal of epidermal ontogenesis is to form a stratum corneum (SC), which is required for post-natal permeability barrier function. The regulation of epidermal ontogenesis is poorly understood, but nuclear hormone receptors have been shown to have an important function. As peroxisome proliferator-activated receptor-delta (PPAR delta) is very abundant in fetal epidermis and PPAR delta activation stimulates differentiation and permeability barrier formation in adults, we hypothesized that PPAR delta might regulate epidermal ontogenesis. Treatment of fetal rat explants with the PPAR delta ligand, GW 610742X, accelerates permeability barrier development, evidenced by a decrease in transepidermal water loss and an enhanced outside-in barrier function, attributable to the presence of more mature lamellar membranes in the SC and enhanced expression of loricrin and involucrin. Similarly, the intra-amniotic administration of GW 610742X also accelerates the formation of the SC and permeability barrier development. Finally, in PPAR delta-deficient mice the formation of the SC and the expression of differentiation-related proteins were delayed on days 16.5 and 17.5 of gestation. However, at later stages (day 18.5 and after birth), there were no differences between wild-type-and PPAR delta-deficient mice, indicating only a transient delay in epidermal ontogenesis. These studies show that PPARd has a role in SC formation and permeability barrier development.