The University of New Mexico School of Medicine, Albuquerque, NM, USA.
Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Exp Dermatol. 2021 Apr;30(4):560-571. doi: 10.1111/exd.14260. Epub 2020 Dec 24.
In the light of substantial discoveries in epithelial and hair pigmentation pathophysiology, this review summarizes the current understanding of skin pigmentation mechanisms. Melanocytes are pigment-producing cells, and their key regulating transcription factor is the melanocyte-specific microphthalmia-associated transcription factor (m-MITF). Ultraviolet (UV) radiation is a unique modulator of skin pigmentation influencing tanning pathways. The delayed tanning pathway occurs as UVB produces keratinocyte DNA damage, causing p53-mediated expression of the pro-opiomelanocortin (POMC) gene that is processed to release α-melanocyte-stimulating hormone (α-MSH). α-MSH stimulates the melanocortin 1 receptor (MC1R) on melanocytes, leading to m-MITF expression and melanogenesis. POMC cleavage also releases β-endorphin, which creates a neuroendocrine pathway that promotes UV-seeking behaviours. Mutations along the tanning pathway can affect pigmentation and increase the risk of skin malignancies. MC1R variants have received considerable attention, yet the allele is highly polymorphic with varied phenotypes. Vitiligo presents with depigmented skin lesions due to autoimmune destruction of melanocytes. UVB phototherapy stimulates melanocyte stem cells in the hair bulge to undergo differentiation and upwards migration resulting in perifollicular repigmentation of vitiliginous lesions, which is under sophisticated signalling control. Melanocyte stem cells, normally quiescent, undergo cyclic activation/differentiation and downward migration with the hair cycle, providing pigment to hair follicles. Physiological hair greying results from progressive loss of melanocyte stem cells and can be accelerated by acute stress-induced, sympathetic driven hyperproliferation of the melanocyte stem cells. Ultimately, by reviewing the pathways governing epithelial and follicular pigmentation, numerous areas of future research and potential points of intervention are highlighted.
鉴于上皮组织和毛发色素沉着的病理生理学方面的重大发现，本文综述了皮肤色素沉着机制的当前认识。黑素细胞是产生色素的细胞，其关键调节转录因子是黑素细胞特异性小眼畸形相关转录因子（m-MITF）。紫外线（UV）辐射是皮肤色素沉着的独特调节剂，影响着晒黑途径。延迟的晒黑途径是由于 UVB 产生角质形成细胞 DNA 损伤，导致 p53 介导的前阿黑皮素原（POMC）基因表达，该基因被加工释放α-促黑素细胞激素（α-MSH）。α-MSH 刺激黑素细胞上的黑素皮质素 1 受体（MC1R），导致 m-MITF 表达和黑色素生成。POMC 切割还释放β-内啡肽，形成促进寻找紫外线的神经内分泌途径。晒黑途径中的突变会影响色素沉着并增加皮肤恶性肿瘤的风险。MC1R 变体受到了相当多的关注，但该等位基因高度多态性，表现型各异。白癜风表现为色素脱失性皮损，是由于黑素细胞的自身免疫破坏。UVB 光疗刺激毛发隆起中的黑素细胞干细胞分化并向上迁移，导致白癜风皮损的毛囊周围再色素沉着，这受到复杂信号的控制。黑素细胞干细胞通常处于静止状态，随着毛发周期经历周期性激活/分化和向下迁移，为毛囊提供色素。生理性毛发变白是由于黑素细胞干细胞的逐渐丧失引起的，并且可以通过急性应激诱导的、交感神经驱动的黑素细胞干细胞过度增殖加速。最终，通过回顾上皮组织和毛囊色素沉着的途径，强调了未来研究和潜在干预点的众多领域。
