Induction of selected lipid metabolic enzymes and differentiation-linked structural proteins by air exposure in fetal rat skin explants

The epidermal permeability barrier of premature infants matures rapidly fol lowing birth. Previous studies suggest that air exposure could contribute t o this acceleration, because: (i) development of a structurally and functio nally mature barrier accelerates when fetal rat skin explants are incubated at an air medium interface, and (ii) occlusion with a water-impermeable me mbrane prevents this acceleration, To investigate further the effects of ai r exposure on epidermal barrier ontogenesis, we compared the activities of several key enzymes of lipid metabolism and gene expression of protein mark ers of epidermal differentiation in fetal rat skin explants grown immersed versus air exposed. The rate-limiting enzymes of cholesterol (HMG CoA reduc tase) and ceramide (serine palmitoyl transferase) synthesis were not affect ed, In contrast, the normal developmental increases in activities of glucos ylceramide synthase and cholesterol sulfotransferase, responsible for the s ynthesis of glucosylceramides and cholesterol sulfate, respectively, were a ccelerated further by air exposure, Additionally, two enzymes required for the final stages of barrier maturation and essential for normal stratum cor neum function, beta-glucocerebrosidase, which converts glucosylceramide to ceramide, and steroid sulfatase, which desulfates cholesterol sulfate, also increased with air exposure. Furthermore, filaggrin and loricrin mRNA leve ls, and filaggrin, loricrin, and involucrin protein levels all increased wi th air exposure, Finally, occlusion with a water-impermeable membrane preve nted both the air-exposure-induced increase in lipid enzyme activity, and t he expression of loricrin, filaggrin, and involucrin, Thus, air exposure st imulates selected lipid metabolic enzymes and the gene expression of key st ructural proteins in fetal epidermis, providing a biochemical basis for air -induced acceleration of permeability barrier maturation in premature infan ts.