Retinoid modulation of connective tissue metabolism in keloid fibroblast cultures

Recent observations have suggested that retinoids might affect the metabolism of the extracellular matrix of connective tissues. In this study, we examined the effects of tretinoin (all-trans-retinoic acid) and isotretinoin (13-cis-retinoic acid) on the production of procollagen in keloid fibroblast cultures that were characterized by enhanced procollagen synthesis in vitro. The activities of three enzymes relevant to connective tissue metabolism, prolyl hydroxylase, collagenase, and an elastaselike neutral protease were also determined. The results demonstrated that collagen production was markedly reduced in cultures treated with either one of the retinoids. The activity of prolyl hydroxylase, a key enzyme in the intracellular biosynthesis of collagen, was not affected, while the production of collagenase was markedly reduced by the retinoids. In contrast, the activity of an elastaselike neutral protease in the cell culture medium was markedly enhanced by both retinoids. The results, therefore, indicate a differential modulation of connective tissue metabolism by retinoids in keloid cell cultures.