The possible role of Wnt/β‐catenin signalling in vitiligo treatment

Abstract

Vitiligo is a common chronic skin disease which has an adverse impact on patients' life. Its pathogenesis is complex, involving autoimmunity and oxidative stress (OS). Autoimmunity leads to the loss of epidermal melanocytes and the formation of the depigmented patches of the disease. Treatment of vitiligo should control the exaggerated immune response to arrest the progress of active disease, and then promote melanocytes to repigmentation. Wnt/β‐catenin signalling pathway has been of recent interest in vitiligo. Wnt/β‐catenin signalling pathway is downregulated in vitiligo. Upregulation of Wnt/β‐catenin signalling possibly control vitiligo autoimmune response by protecting melanocyte from OS damage, inhibiting CD8+ T cell effector cell differentiation and enhancing Treg. Wnt/β‐catenin signalling plays a critical role in the melanocyte regeneration by driving the differentiation of melanocyte stem cells (McSCs) into melanocytes. Promoting Wnt/β‐catenin signalling can not only arrest the progress of active disease of vitiligo but also promote repigmentation. Some of the main effective therapies for vitiligo are likely to work by activating Wnt/β‐catenin signalling. Agents that can enhance the effect of Wnt/β‐catenin signalling may become potential candidates for the development of new drugs for vitiligo treatment.

Topical ruxolitinib: A new treatment for vitiligo

“…ritlecitinib, 52,53 upadacitinib 54 and baricitinib 55 ). Furthermore, other potential therapeutic targets are being currently evaluated, including Wnt‐signalling, 56 IL‐15 pathway 57 and the heat shock protein 70 58 …”

“…ritlecitinib, 52,53 upadacitinib 54 and baricitinib 55 ). Furthermore, other potential therapeutic targets are being currently evaluated, including Wnt-signalling, 56 IL-15 pathway 57 and the heat shock protein 70. 58 There is still considerable uncertainty concerning the duration of topical ruxolitinib treatment required to ensure the best pigmentation, and the durability of repigmentation after its withdrawal.…”

Melanocyte stem cells in the skin: Origin, biological characteristics, homeostatic maintenance and therapeutic potential

“…For example, Wnt/β-catenin signalling not only prevents the progression of active vitiligo but also promotes white patch pigmentation. 81 These results suggest that drugs or compounds with the function of activating Wnt/βcatenin signalling may be potential candidates for the development of new therapeutic agents for vitiligo. Furthermore, other skin cells neighbouring MSCs, including keratinocytes, fibroblasts and endothelial cells, may play an important role in pigmentation by regulating MSCs.…”

“… 38 Furthermore, intervening in MSC‐associated signalling pathways may promote vitiligo repigmentation. For example, Wnt/β‐catenin signalling not only prevents the progression of active vitiligo but also promotes white patch pigmentation 81 . These results suggest that drugs or compounds with the function of activating Wnt/β‐catenin signalling may be potential candidates for the development of new therapeutic agents for vitiligo.…”

The role of aryl hydrocarbon receptor in vitiligo: a review

“…AhR can upregulate Nrf1 and its downstream TFAM expression to promote mitochondrial biogenesis and avoid oxidative damage in mitochondria and melanocytes ( 36 ). In addition, AhR signaling probably crosstalk with PI3K/Akt and Wnt/β-catenin pathway as well, which are related to reducing oxidative stress-induced melanocyte destruction ( 35 , 40 , 41 ). AhR can upregulate the pathways of PI3K/Akt and Wnt/β-catenin, and activate their downstream signal Nrf2, thereby reducing oxidative stress ( Figure 1 ).…”