SUCCESSIVE ALTERATION AND RECOVERY OF EPIDERMAL DIFFERENTIATION AND MORPHOGENESIS AFTER SPECIFIC UVB-DAMAGES IN SKIN RECONSTRUCTED IN-VITRO

The sequence of events affecting skin morphogenesis occurring after a single exposure to UVB was investigated on a model of human skin recon structed in vitro. The biologically efficient dose (BED) able to induc e the early UVB-DNA damages such as pyrimidine dimers, sunburn cells, and apoptotic keratinocytes was determined as 50 mJ/cm(2). The subsequ ent changes induced during a period of 14 days following irradiation w ere analyzed. Up to Day 3, an epidermal disorganization led to a parak eratotic epidermis characterized by nucleated horny layers, as well as the down regulation of major markers of keratinocyte differentiation such as keratin 10, loricrin, filaggrin, and the keratinocyte transglu taminase (type I). On the contrary, the expression of involucrin and s pr1 seemed to be unaffected, indicating distinct responses to UVB of p roteins involved in keratinocyte differentiation. A progressive regene ration of normal epidermal morphogenesis begins from Day 4 leading to the normalization of keratinocyte differentiation at Day 10 to 14. In parallel, epidermal proliferation was increased. Taken together, these findings show that in skin reconstructed in vitro, UVB exposure leads to major epidermal developmental changes characterized by (i) an earl y apoptotic process, (ii) a subsequent down-regulation of specific ker atinocyte differentiation markers, and (iii) the recovery of both the early and delayed effects resulting in normal epidermal morphogenesis. (C) 1997 Academic Press.