534 Vitiligo: Studying the dermal compartment

Abstract

Homeostasis of pigmentary system is regulated by strictly balanced interactions at both molecular and cellular level and a multitude of messengers and growth factors released by epidermal and dermal cells regulate melanocyte activities and consequently skin pigmentation. Vitiligo is characterized by the progressive disappearance of melanocytes. Increasing evidences are currently highlighting an intrinsic metabolic impairment of melanocytes, favouring the increase of intracellular oxidative stress, which, in turn, may promote the onset of a premature senescent-like phenotype. Despite the important role of the dermis in regulating melanocyte physiology, few data have evaluated its involvement in vitiligo. The aim of our study was to investigate the dermal compartment of non lesional vitiligo skin, focusing on the features of extracellular matrix proteins and fibroblasts. We employed primary cultures of non lesional vitiligo fibroblasts and performed a parallel ex vivo evaluation on skin biopsies collected from the same patients from whom the cells were derived. Our results demonstrate that vitiligo fibroblasts display increased basal ROS levels associated with the up-modulation of stress-induced markers, e.g. p53 and its target gene GADD45. The higher intrinsic oxidative stress favours the transition of fibroblasts into a myofibroblasts-like phenotype, as assessed by the positive expression of markers related to myofibroblasts including alpha-smooth muscle actin, the glycoprotein fibronectin, the intermediate filament associated protein vimentin and the secretory proteins interleukin IL-6 and hepatocyte growth factor. The results point to the involvement of the entire skin in vitiligo, showing the presence of modifications not restricted to melanocytes, which constitute the long-established major player of the disease, but extended to the dermis. The focus on normal appearing skin may therefore allow to recognize the appearance of cellular phenomena before the clear clinical onset of the disease and possibly restrict the spread of the lesions.