Influence of retinoic acid on the ultrastructure and hyaluronic acid synthesis of adult human epidermis in whole skin organ culture.

Normal human skin was maintained in organ culture under chemically defined conditions. All-trans retinoic acid was added to the culture medium at the final concentration of 5 mumol/l. After 5 days in culture samples were either harvested for electron microscopy or labeled with 3H-glucosamine for 24 h. After labeling, epidermis was separated from dermis and both tissue compartments were analyzed for the content of 3H-labeled glycosaminoglycans (GAGs) using CPC-precipitation and thin layer chromatography after enzymatic degradation into specific disaccharides. Retinoic acid caused a marked change in the epidermal tissue architecture. The epidermal cells were flattened and contained fewer desmosomes and tonofilaments than control explants. Retinoic acid induced accumulation of fine granular material in the intercellular spaces in the upper, and less dense, flocculent material in the lower epidermis. The analysis of 3H-glycosaminoglycans showed that in the epidermis retinoic acid elevated the amount of labeled hyaluronate by 70%, whereas sulfated GAGs were not significantly increased. In dermis the incorporation of 3H-glucosamine into neither hyaluronate nor sulfated GAGs was stimulated by the retinoic acid. It is concluded that retinoic acid significantly modifies the differentiation of normal adult human epidermis by decreasing cytoskeleton components and by inducing the synthesis of new intercellular material, at least a part of which is hyaluronic acid. As a consequence, the cohesion between the epidermal cells was apparently weakened.