Protease-activated receptor-2 downregulation is associated to vitiligo lesions

Protease-activated receptors (PARs) are members of the G protein-coupled receptor superfamily that are activated by the proteolytic cleavage of their amino terminal domain. PARs are expressed in several tissues by a variety of cells and are implicated in numerous biologic effects, including coagulation, inflammation, mitogenesis and cell proliferation. PAR-2 is expressed by keratinocytes in the epidermis, being activated by trypsin-like enzymes such as mast-cell tryptase, and it affects epidermal pigmentation via modulation of melanosome uptake in vivo. Because vitiligo is a skin disorder characterized by melanocyte impairment and loss of melanin in keratinocytes, PAR-2 may be involved in this condition. Twenty-three vitiligo patients with active disease were studied. PAR-2 expression was significantly lower in lesional versus perilesional and normal epidermis, by both immunohistochemistry and molecular biology. Cultured keratinocytes from depigmented lesions exhibited a lower PAR-2 function compared to normal keratinocytes. PAR-2 expression appears reduced in vitiligo and its down-regulation seems associated with pigment loss. These data confirm the involvement of keratinocyte function in vitiligo process.