Department of Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
Metabolic and Genetic Regulation of Ageing, Max Planck Institute for Biology of Ageing, Cologne, Germany.
Exp Dermatol. 2021 Dec;30(12):1800-1806. doi: 10.1111/exd.14406. Epub 2021 Jun 22.
Vitiligo is an autoimmune disease characterized by depigmented patches of skin due to loss of the pigment-producing melanocytes. No cure exists for vitiligo. The available treatments are inefficient for many patients, suggesting that universal treatment approaches may be inappropriate. Deeper understanding of the mechanistic basis for variability in vitiligo aetiologies is necessary. Genetic mutations in neuropeptide Y (NPY), a widely distributed protein, are associated with increased NPY expression and increased susceptibility for vitiligo. NPY is also upregulated in the circulation and lesional skin of some vitiligo patients. However, the contributions of NPY to melanocyte pathology are not understood, and presently there are no models with which to investigate this possibility. In this study, we employed NPY-overexpressing mice to explore the role of NPY in melanocyte dysfunction. Our results show that NPY overexpression induces progressive hair greying (depigmentation) due to premature depletion of follicular melanocyte stem cells. Additionally, NPY transcripts and protein are elevated in the skin and melanocytes of these mice, respectively, suggesting that these effects may be mediated locally. Together, these results suggest that supraphysiological levels of NPY in the skin can induce melanocyte dysfunction, thus identifying this mouse line as a novel model to study NPY-mediated melanocyte pathology.
白癜风是一种自身免疫性疾病，其特征是由于产生色素的黑素细胞丧失而导致皮肤脱色斑块。目前尚无治愈白癜风的方法。现有的治疗方法对许多患者效果不佳，这表明普遍的治疗方法可能并不合适。需要更深入地了解白癜风发病机制的变异的机制基础。神经肽 Y (NPY) 是一种广泛分布的蛋白质，其基因突变与 NPY 表达增加和白癜风易感性增加有关。NPY 在一些白癜风患者的循环和皮损皮肤中也上调。然而，NPY 对黑素细胞病理学的贡献尚不清楚，目前尚无模型可用于研究这种可能性。在这项研究中，我们使用 NPY 过表达小鼠来探索 NPY 在黑素细胞功能障碍中的作用。我们的结果表明，NPY 过表达导致毛囊黑素细胞干细胞过早耗竭，从而诱导进行性头发变白（脱色）。此外，这些小鼠的皮肤和黑素细胞中分别升高了 NPY 转录本和蛋白，这表明这些影响可能是局部介导的。总之，这些结果表明，皮肤中超生理水平的 NPY 可诱导黑素细胞功能障碍，从而确定了这条小鼠品系是研究 NPY 介导的黑素细胞病理学的一种新模型。
