Repeated exposure of human fibroblasts to UVR induces secretion of stem cell factor and senescence.

ABSTRACT

BACKGROUND: Some of chronic hyperpigmentary diseases, such as melasma, induced by multiple factors including chronic sunlight exposure, can recur even after chemical epidermal removal. Dermal factors may be involved in the pathogenesis of melasma. Changes in dermal fibroblasts resulting from chronic sun exposure might cause melanocytes to synthesize melanin in the epidermis. OBJECTIVE: This study aimed at determining the effects of repetitive ultraviolet (UV) radiation on cultured fibroblasts and the secretion of melanogenic factors. METHODS: Cultured human fibroblasts were exposed to ultraviolet A (UVA) or ultraviolet B (UVB) for five consecutive days. After each irradiation, the supernatant medium was isolated from each dish and measured for levels of stem cell factor (SCF) and hepatocyte growth factor using an ELISA kit assay. To assess the effect of the keratinocyte-derived factors on fibroblast-secretion of SCF and hepatocyte growth factor, we added supernatants of the UV-irradiated keratinocytes to the non-irradiated fibroblasts. Finally, the irradiated fibroblasts were stained with senescence associated-ß-galactosidase to assess their senescent change. RESULTS: Fibroblasts irradiated with UVA or UVB for five consecutive days, secreted SCF at levels that increased with repeated UVA or UVB exposure. Conditioned culture medium from UV-irradiated keratinocytes also induced SCF release from fibroblasts, depending on the number of UV exposures. UVA- or UVB-irradiated fibroblasts stained positive for senescence associated-ß-galactosidase, and the staining intensity increased with repeated exposure. CONCLUSION: These results suggest that fibroblast senescence and increased SCF secretion after repeated UV irradiation may be related to the pathogenesis of recurring hyperpigmentation disorders induced by chronic sun exposure.