Previously, it was demonstrated that a hyperpigmented melasma lesion is characterized by increased vasculature, which may play a role in the development of hyperpigmentation. Herein, I report the in vitro evidence of the vascular modulation of skin pigmentation. In the presence of endothelial cells, the pigmentation of melanocytes and of ex vivo cultured human skin was reduced. Contrary to non-stimulated cells, UV-irradiated endothelial cells showed stimulatory action on skin pigmentation. However, other stimulation, such as VEGF treatment and hypoxic condition, did not shown any significant effect. Gene expression profiling was undertaken to identify melanogenic factors from UV-irradiated endothelial cells. Endothelin-1 (ET-1) was found to be up-regulated, and the increased pigmentation elicited by UV-irradiated endothelial cell-derived conditioned medium was prevented by inhibiting the ET-1 receptor. Our study suggests that endothelial cells have a negative effect on pigmentation. However, their effect differs after they are irradiated with UV, as they then positively influence the induction of melanogenesis. This may play a role in the development of hyperpigmentary disorders.
