SIRT1 regulates MAPK pathways in vitiligo skin: insight into the molecular pathways of cell survival

ABSTRACT Vitiligo is an acquired and progressive hypomelanotic disease that manifests as circumscribed depigmented patches on the skin. The etiology of vitiligo remains unclear, but recent experimental data underlines the interactions between melanocytes and other typical skin cells, particularly keratinocytes. Our previous results indicate that keratinocytes from perilesional skin show the features of damaged cells. Sirtuins, well known modulators of lifespan in many species, have a role in gene repression, metabolic control, apoptosis and cell survival, DNA repair, development, inflammation, neuroprotection, and healthy aging. In the literature there is no evidence for SIRT1 signaling in vitiligo and its possible involvement in disease progression. Here, biopsies were taken from the perilesional skin of 16 patients suffering from nonsegmental vitiligo and SIRT1 signaling was investigated in these cells. For the first time, a new SIRT1/Akt/MAPK signaling has been revealed in vitiligo. SIRT1 regulates MAPK pathway via Akt-ASK1 and downregulates pro-apoptotic molecules, leading to decreased oxidative stress and apoptotic cell death in perilesional vitiligo keratinocytes. We therefore propose SIRT1 activation as a novel way of protecting perilesional vitiligo keratinocytes from damage.