RETINOIDS AFFECT COLLAGEN-SYNTHESIS THROUGH INHIBITION OF ASCORBATE-INDUCED LIPID-PEROXIDATION IN CULTURED HUMAN DERMAL FIBROBLASTS

Ascorbate has been shown to stimulate collagen synthesis in cultured human dermal fibroblasts by increasing transcription of the collagen genes. In the present studies, ascorbate stimulates lipid peroxidation at concentrations similar to those necessary to affect collagen synthesis. Molecules which inhibit lipid peroxidation, such as propyl gallate, cobalt chloride, and α-naphthol, also inhibit collagen synthesis, suggesting a correlation between the two phenomena. Retinoic acid and some synthetic retinoids have previously been shown to inhibit collagen synthesis in cultured human dermal fibroblasts. In our studies two different retinoids, at similar concentrations, inhibit both ascorbate-stimulated lipid peroxidation and collagen synthesis. Since high concentrations of retinoids were required, the ability of retinoids to inhibit the oxidant effect of ascorbate, and not their receptor-mediated activity, may be responsible for their effect on collagen synthesis. © 1990.