Effect of vitamin A acid on homeostasis and differentiation of epidermal cells cultured on collagen.

Cultured guinea pig epidermal cells were treated with vitamin A acid (VA;2, 5, 10 micrograms/ml) and controlled by autoradiography and histochemical method. Cells attached to the bottom of the plates were counted and their number correlated with the number of cells sloughed off into the medium (A/D ratio). VA reduced the size of multilayered cell colonies, favoured cell spreading and accelerated confluence. It altered the mode of shedding since the cells sloughed off into the medium as isolated cells rather than cell complexes, as in untreated controls. It increased the A/D ratio in early cell cultures and decreased the A/D ratio in late cell culture. The higher the concentration of VA, the earlier and more prominent was the decrease of the A/D ratio. Low concentration of VA (2micrograms/ml) given once at seeding favoured the formation of keratohyalin and cornified envelopes whereas high concentration (5, 10micrograms/ml) given continuously prevented their formation and caused mucoid vacuolar degeneration of single cells. VA inhibited complete keratinization in all cases, but appeared to allow pre-keratinization, particularly at low concentrations. The results indicate that VA controls epidermal homeostasis in vitro by its influence on both proliferation and shedding. Its effect on the markers of differentiation is heterogeneous since it prevented keratinization in every case, but induced keratohyalin formation under certain conditions.