The ultimate objectives of the proposed research are to discover the role of lipids in normal epidermal differentiation and to determine to what extent disorders of keratinization in human skin can be attributed to faulty epidermal lipid metabolism. As a basis for understanding the metabolism and physiological role of epidermal polar lipids, studies are proposed which will identify each of the classes of polar lipid present in full thickness epidermis of the pig, including the ceramides, glucosylceramides, gangliosides and steryl sulfates. The presence and composition of these lipids in isolated stratum corneum and in exfoliated epidermal cells will also be determined. This will allow hypotheses to be generated on the ossible role of specific lipid structures in the processes of keratinization, water barrier formation and maintenance, and normal desquamation, in mammalian epidermis. Additional insight into these questions will be sought by examining the lipid composition in the living and cornified layers of epidermis from other orders of vertebrates, including birds, reptiles, amphibians and fish. The lipid compositions will be compared with the known differences in ultrastructural morphology between the epithelia of the several orders. This is expected to further provide for formulation of hypotheses on the specific roles of individual polar lipids in epidermal structures, especially the lamellar bodies of the granular cells and the intercellular lamellae of the stratum corneum. In view of the know effects of dietary linoleic acid deficiency on the structural integrity and water barrier properties of mammalian epidermis, the effect of such deficiency on the composition of epidermal lipids in pigs will be studied. Additional studies of this kind using rats will also be done, for correlation with the results of other investigators. For delineation of the pathways of lipid metabolism in epidermis, radiotracer studies will be performed, using 14C-labelled acetate, glucose, palmitate, linoleate and serine. The substrates will be incorporated in vivo by intradermal injection and possibly also by percutaneous absorption while the normal barrier is reduced by dimethylsulfoxide. The experimental animals to be used in these studies will be the horse, pig and rat. During these studies, hypotheses and experimental methods will be developed for the investigation of scaling disorders of the skin in human subjects.
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