Becatti Matteo, Fiorillo Claudia, Barygina Victoria, Cecchi Cristina, Lotti Torello, Prignano Francesca, Silvestro Agrippino, Nassi Paolo, Taddei Niccolò
Department of Biochemical Sciences, University of Florence, Florence, Italy.
J Cell Mol Med. 2014 Mar;18(3):514-29. doi: 10.1111/jcmm.12206. Epub 2014 Jan 10.
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.
白癜风是一种后天性进行性色素减退性疾病，表现为皮肤上出现边界清晰的色素脱失斑。白癜风的病因尚不清楚，但最近的实验数据强调了黑素细胞与其他典型皮肤细胞，尤其是角质形成细胞之间的相互作用。我们之前的结果表明，皮损周围皮肤的角质形成细胞呈现出受损细胞的特征。沉默信息调节因子2相关酶1（Sirtuins，简称SIRT1）是许多物种中著名的寿命调节因子，在基因抑制、代谢控制、细胞凋亡与细胞存活、DNA修复、发育、炎症、神经保护和健康衰老等方面发挥作用。文献中没有关于白癜风中SIRT1信号及其可能参与疾病进展的证据。在此，我们从16例非节段型白癜风患者的皮损周围皮肤取材，对这些细胞中的SIRT1信号进行了研究。首次在白癜风中发现了一种新的SIRT1/Akt信号通路，Akt也被称为蛋白激酶B（PKB）/丝裂原活化蛋白激酶（MAPK）信号通路。SIRT1通过Akt-凋亡信号调节激酶-1调节MAPK通路，并下调促凋亡分子，从而降低皮损周围白癜风角质形成细胞的氧化应激和凋亡性细胞死亡。因此，我们提出激活SIRT1是保护皮损周围白癜风角质形成细胞免受损伤的一种新方法。
