SIRT1 regulates MAPK pathways in vitiligo skin: insight into the molecular pathways of cell survival
Article first published online: 10 JAN 2014
© 2013 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Journal of Cellular and Molecular Medicine
Volume 18, Issue 3, pages 514–529, March 2014
How to Cite
Becatti, M., Fiorillo, C., Barygina, V., Cecchi, C., Lotti, T., Prignano, F., Silvestro, A., Nassi, P. and Taddei, N. (2014), SIRT1 regulates MAPK pathways in vitiligo skin: insight into the molecular pathways of cell survival. Journal of Cellular and Molecular Medicine, 18: 514–529. doi: 10.1111/jcmm.12206
- Issue published online: 27 FEB 2014
- Article first published online: 10 JAN 2014
- Manuscript Accepted: 4 NOV 2013
- Manuscript Received: 4 FEB 2013
- Fondazione Cassa di Risparmio di Pistoia e Pescia
- Ente Cassa di Risparmio di Firenze
- MAPK ;
- oxidative stress
Vitiligo is an acquired and progressive hypomelanotic disease that manifests as circumscribed depigmented patches on the skin. The aetiology of vitiligo remains unclear, but recent experimental data underline 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 (silent mating type information regulation 2 homolog) 1, 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 ageing. In the literature there is no evidence for SIRT1 signalling in vitiligo and its possible involvement in disease progression. Here, biopsies were taken from the perilesional skin of 16 patients suffering from non-segmental vitiligo and SIRT1 signalling was investigated in these cells. For the first time, a new SIRT1/Akt, also known as Protein Kinase B (PKB)/mitogen-activated protein kinase (MAPK) signalling has been revealed in vitiligo. SIRT1 regulates MAPK pathway via Akt-apoptosis signal-regulating kinase-1 and down-regulates 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.