Endothelial Cells Promote Pigmentation Through Endothelin Receptor B Activation

Regazzetti C, De Donatis GM, Ghorbel HH, Cardot-Leccia N, Ambrosetti D, Bahadoran P, Chignon B, Lacour JP, Ballotti R, Mahns A, Passeron T

J. Invest. Dermatol. 2015 Aug;

Abstract

PMID: 26308584

Findings of increased vascularization in melasma lesions and hyperpigmentation in acquired bilateral telangiectatic macules suggested a link between pigmentation and vascularization. Using high-magnification digital epiluminescence dermatoscopy, laser confocal microscopy, and histological examination, we showed that benign vascular lesions of the skin have restricted but significant hyperpigmentation compared to the surrounding skin. We then studied the role of microvascular endothelial cells in regulating skin pigmentation using an in vitro co-culture model using endothelial cells and melanocytes. These experiments showed that endothelin 1 released by microvascular endothelial cells induces increased melanogenesis signaling, characterized by microphthalmia-associated transcription factor phosphorylation and increased tyrosinase and dopachrome tautomerase levels. Immunostaining for endothelin 1 in vascular lesions confirmed the increased expression on the basal layer of the epidermis above small vessels compared to perilesional skin. Endothelin acts through the activation of endothelin receptor B and the MAPKs, ERK1/2 and p38, to induce melanogenesis. Finally, culturing of reconstructed skin with microvascular endothelial cells led to increased skin pigmentation that could be prevented by inhibiting EDNRB. Taken together these results demonstrated the role of underlying microvascularization in skin pigmentation, a finding that could open new fields of research for regulating physiological pigmentation and for treating pigmentation disorders such as melasma.Journal of Investigative Dermatology accepted article preview online, 26 August 2015. doi:10.1038/jid.2015.332.