Vitiligo: Translational research and effective therapeutic strategies

Meng

2023

Acad Dermatol Venereol

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.

Section: Ac Ti Vati Ng W N T/β -Cate N I N Signa L Li Ng I N Th E Tr ...mentioning

confidence: 99%

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

Meng

2023

Acad Dermatol Venereol

“…3,4 The diagnosis of vitiligo can be made from clinical examination and additional laboratory tests are usually needed only for confirmation. 5 The pathogenesis of SV, including neuropeptide, somatic mosaicism, and microvascular skin horning, which eventually cause melanocyte damage, is better known than that of NSV. [6][7][8] Otherwise, NSV pathogenesis is still multifactorial and polygenic.…”

Section: Introductionmentioning

confidence: 99%

Comparison of BiP and HSP70i as markers of unfolded protein response (UPR) in segmental and nonsegmental vitiligo

et al. 2023

Background: Unfolded protein response (UPR) is a misfolded protein that occurs because oxidative stress disrupts cellular redox potential that extends to the endoplasmic reticulum (ER). Binding immunoglobulin protein (BiP) and inducible heat shock protein (HSP70i) as ER chaperons play critical roles in melanocyte apoptosis. Our study aims to compare BiP and HSP70i as markers of UPR in patients with segmental vitiligo (SV) and non-segmental vitiligo (NSV). Methods: The subjects were composed of 64 patients diagnosed with vitiligo, of whom 33 had NSV and 31 had SV. Skin biopsy and immunofluorescence were performed. We used BiP and HSP70i as markers of UPR. Descriptive statistics were used to analyze the data. Results: UPR-BiP expression and UPR-HSP70i in the SV group was 2.66 ± 3.07 and 3.85 ± 4.92, respectively, with a p-value of 0.001 (<α = 0.05). In the NSV group UPR-BiP expression and UPR-HSP70i was 12.55 ± 11.85 and 14.79 ± 14.72 respectively, with a p-value of 0.001 (<α = 0.05). UPR expression using the HSP70i marker in both NSV and SV groups was higher than it was using the BiP marker. The relationship between UPR-HSP70i expression and UPR-BiP expression in the SV and NSV group was significant (p <0.05) and positive. Conclusions: HSP70i is superior to BiP as a marker for expressing UPR.

“…Vitiligo is a common depigmentation disease characterized by progressive destruction and disappearance of epidermal melanocytes, with an estimated prevalence of 0.1–2% ( 1 ). It is extensively accepted that vitiligo seriously affects patients’ quality of life and causes serious psychological burden ( 2 ). The clinical treatment of vitiligo is limited because of its complex pathogenesis ( 1 ).…”

Section: Introductionmentioning

confidence: 99%

Peripheral Blood of Vitiligo Patients-Derived Exosomal MiR-21-5p Inhibits Melanocytes Melanogenesis via Targeting SATB1

Zhang¹,

Guo²,

Wang³

et al. 2022

ijph

Background: Vitiligo is a common depigmentation disease characterized by progressive destruction and disappearance of epidermal melanocytes. Exosomes have been discovered to regulate the pigment status of melanocytes. We aimed to explore the role of exosomes from peripheral blood of vitiligo patients on melanogenesis. Methods: Human melanocytes cell line PIG1 was treated with exosomes from the healthy volunteers or exosomes from the vitiligo patients referred to the Department of Dermatology, Children’s Hospital Affiliated to Zhengzhou University, China and transfected with miR-21-5p mimic or inhibitor. Exosome labeling assay was used to assess whether exosomes were absorbed by melanocytes. Melanin content and tyrosinase activity assays were performed to investigate melanogenesis in melanocytes. The levels of melanogenesis-related genes and proteins were detected by RT-qPCR and western blot assays. Dual-luciferase reporter assay was performed to confirm the relationship between miR-21-5p and special AT-rich sequence binding protein-1 (SATB1). Results: Exosomes from peripheral blood of vitiligo patients were transferred into melanocytes and suppressed melanin content, tyrosinase activity and melanogenesis-related genes and proteins levels. Besides, miR-21-5p was highly expressed in exosomes from peripheral blood of vitiligo patients. The results of the gain- and loss-of-function experiments demonstrated that miR-21-5p inhibited the melanogenesis of melanocytes. Furthermore, miR-21-5p inhibitor abolished the inhibitory role of exosomes from peripheral blood of vitiligo patients. Subsequently, miR-21-5p directly targeted SATB1 in melanocytes. Furthermore, overexpression of SATB1 reversed the inhibitory roles of miR-21-5p mimic on melanin content, tyrosinase activity, and melanogenesis-related protein expression. Conclusion: Peripheral blood of vitiligo patients-derived exosomal miR-21-5p inhibited melanocytes melanogenesis via targeting SATB1.