Identification of TYR, TYRP1, DCT and LARP7 as related biomarkers and immune infiltration characteristics of vitiligo via comprehensive strategies

Zhang, Jiayu; Yu, Rongguo; Guo, Xiaoyu; Zou, Yuanxia; Chen, Sixuan; Zhou, Kai; Chen, Yi; Li, YongRong; Gao, Su; Wu, Yue

doi:10.1080/21655979.2021.1933743

Cited by 21 publications

(11 citation statements)

References 46 publications

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“…Dilatation of the ER occurs because of the buildup of misfolded proteins, perpetuating ER stress and oxidative stress [ 73 , 74 ]. Additional instability of tyrosinase-related protein-1 (TYRP1), which is required for melanogenesis, leads to accumulation of melanin intermediates in patients with vitiligo [ 75 , 76 , 77 ]. Melanin intermediates, together with other stressors such as heat shock or ROS, disrupt the protein folding process in the ER, activating the unfolded protein response (UPR) and integrated stress response (ISR) [ 78 , 79 ].…”

Section: Current Concepts In Immunopathogenesis Of Vitiligomentioning

confidence: 99%

Current Concepts of Vitiligo Immunopathogenesis

et al. 2022

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Vitiligo is an acquired immune-mediated disorder of pigmentation clinically characterized by well-defined depigmented or chalk-white macules and patches on the skin. The prevalence of vitiligo varies by geographical area, affecting 0.5% to 2% of the population. The disease imposes a significant psychological burden due to its major impact on patients’ social and emotional aspects of life. Given its autoimmune background, vitiligo is frequently associated with other autoimmune diseases or immune-mediated diseases. Vitiligo is a multifaceted disorder that involves both genetic predisposition and environmental triggers. In recent years, major predisposing genetic loci for the development of vitiligo have been discovered. The current findings emphasize the critical role of immune cells and their mediators in the immunopathogenesis of vitiligo. Oxidative-stress-mediated activation of innate immunity cells such as dendritic cells, natural killer, and ILC-1 cells is thought to be a key event in the early onset of vitiligo. Innate immunity cells serve as a bridge to adaptive immunity cells including T helper 1 cells, cytotoxic T cells and resident memory T cells. IFN-γ is the primary cytokine mediator that activates the JAK/STAT pathway, causing keratinocytes to produce the key chemokines CXCL9 and CXCL10. Complex interactions between immune and non-immune cells finally result in apoptosis of melanocytes. This paper summarizes current knowledge on the etiological and genetic factors that contribute to vitiligo, with a focus on immunopathogenesis and the key cellular and cytokine players in the disease’s inflammatory pathways.

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Section: Current Concepts In Immunopathogenesis Of Vitiligomentioning

confidence: 99%

Current Concepts of Vitiligo Immunopathogenesis

et al. 2022

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“…Vitiligo is one of the most common depigmentation skin diseases characterized by abnormal regulation of melanocytes melanogenesis ( 21 ). For example, the accumulation of abnormal melanosome structures in vitiligo melanocytes is associated with polymorphism in the tyrosinase gene ( 22 ). Furthermore, evidence has shown that a positive CD8+T cell could be isolated from peripheral blood of patients with vitiligo, which kills melanocytes in vitro ( 23 ).…”

Section: Discussionmentioning

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

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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.

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“…It was a practicality for most biological studies (Fortino et al, 2020;Shen et al, 2020;Unger et al, 2020). Among these important transcriptomic features, several top-ranked variables were closely related to the melanogenesis and immune characteristics, which was the main phenotypes of vitiligo (Picardo et al, 2015;Niu and Aisa, 2017;Pu et al, 2021;Zhang et al, 2021). Moreover, we constructed a more comprehensive VitNet and obtained 160 articulation proteins by the GAPR method.…”

Section: Discussionmentioning

confidence: 99%

Development of a Multi-Target Strategy for the Treatment of Vitiligo via Machine Learning and Network Analysis Methods

et al. 2021

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Vitiligo is a complex disorder characterized by the loss of pigment in the skin. The current therapeutic strategies are limited. The identification of novel drug targets and candidates is highly challenging for vitiligo. Here we proposed a systematic framework to discover potential therapeutic targets, and further explore the underlying mechanism of kaempferide, one of major ingredients from Vernonia anthelmintica (L.) willd, for vitiligo. By collecting transcriptome and protein-protein interactome data, the combination of random forest (RF) and greedy articulation points removal (GAPR) methods was used to discover potential therapeutic targets for vitiligo. The results showed that the RF model performed well with AUC (area under the receiver operating characteristic curve) = 0.926, and led to prioritization of 722 important transcriptomic features. Then, network analysis revealed that 44 articulation proteins in vitiligo network were considered as potential therapeutic targets by the GAPR method. Finally, through integrating the above results and proteomic profiling of kaempferide, the multi-target strategy for vitiligo was dissected, including 1) the suppression of the p38 MAPK signaling pathway by inhibiting CDK1 and PBK, and 2) the modulation of cellular redox homeostasis, especially the TXN and GSH antioxidant systems, for the purpose of melanogenesis. Meanwhile, this strategy may offer a novel perspective to discover drug candidates for vitiligo. Thus, the framework would be a useful tool to discover potential therapeutic strategies and drug candidates for complex diseases.

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Identification of TYR, TYRP1, DCT and LARP7 as related biomarkers and immune infiltration characteristics of vitiligo via comprehensive strategies

Cited by 21 publications

References 46 publications

Current Concepts of Vitiligo Immunopathogenesis

Current Concepts of Vitiligo Immunopathogenesis

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

Development of a Multi-Target Strategy for the Treatment of Vitiligo via Machine Learning and Network Analysis Methods

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