Effect of donor age and prior sun exposure on growth inhibition of cultured human dermal fibroblasts by all trans-retinoic acid.

The effect of retinoic acid on human fibroblasts was studied in a cell culture model of chronologic aging and photoaging. During early exponential phase, all trans-retinoic acid significantly stimulated growth rate of adult arm-derived dermal fibroblasts but not of newborn or adult foreskin-derived fibroblasts. Retinoic acid also significantly reduced saturation density in most young adult arm-derived lines and all 24 lines derived from old adult arm and foreskin. However, four of ten young adult outer arm (relatively sun-exposed) and one of ten young adult inner arm (relatively sun-protected) fibroblasts lines increased their saturation density in response to retinoic acid. These data suggest that prior sun exposure and/or donor age may influence cellular responsiveness to retinoic acid. Neither the stimulatory nor the inhibitory effect of retinoic acid could be attributed to cell density, to breakdown of retinoic acid in culture, to nutrient depletion or to serum dependency. However, stationary phase fibroblasts from all sites (foreskin, inner and outer arm) showed an increase in filopodia and in intracellular actin after treatment with retinoic acid that was roughly proportional to the degree of growth inhibition, irrespective of donor age. We suggest that retinoic acid induces premature density dependent growth inhibition at least in part by increasing filopodia-mediated cell contact that is in turn directly related to an increase in fibrillar actin.