白癜风患者外周血来源的外泌体 miR-21-5p 通过靶向 SATB1 抑制黑素细胞的黑素生成。
Peripheral Blood of Vitiligo Patients-Derived Exosomal MiR-21-5p Inhibits Melanocytes Melanogenesis via Targeting SATB1.
作者信息
Zhang Change, Guo Wu, Wang Sheng, Di Yuzi, Wu Dengting
机构信息
Department of Dermatology, Children's Hospital Affiliated to Zhengzhou University, 450018, Henan Province, Zhengzhou, China.
出版信息
Iran J Public Health. 2022 Dec;51(12):2706-2716. doi: 10.18502/ijph.v51i12.11461.
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.
背景
白癜风是一种常见的色素脱失性疾病，其特征为表皮黑素细胞进行性破坏和消失。已发现外泌体可调节黑素细胞的色素状态。我们旨在探讨白癜风患者外周血来源的外泌体在黑素生成中的作用。
方法
用来自健康志愿者的外泌体或来自郑州大学附属儿童医院皮肤科白癜风患者的外泌体处理人黑素细胞系PIG1，并转染miR-21-5p模拟物或抑制剂。采用外泌体标记试验评估黑素细胞是否吸收外泌体。进行黑色素含量和酪氨酸酶活性测定以研究黑素细胞中的黑素生成。通过RT-qPCR和蛋白质印迹试验检测黑素生成相关基因和蛋白质的水平。进行双荧光素酶报告基因试验以确认miR-21-5p与富含AT序列结合蛋白1（SATB1）之间的关系。
结果
白癜风患者外周血来源的外泌体被转移到黑素细胞中，并抑制了黑色素含量、酪氨酸酶活性以及黑素生成相关基因和蛋白质水平。此外，miR-21-5p在白癜风患者外周血来源的外泌体中高表达。功能获得和功能丧失实验结果表明，miR-21-5p抑制黑素细胞的黑素生成。此外，miR-21-5p抑制剂消除了白癜风患者外周血来源外泌体的抑制作用。随后，miR-21-5p在黑素细胞中直接靶向SATB1。此外，SATB1的过表达逆转了miR-21-5p模拟物对黑色素含量、酪氨酸酶活性和黑素生成相关蛋白表达的抑制作用。
结论
白癜风患者外周血来源的外泌体miR-21-5p通过靶向SATB1抑制黑素细胞黑素生成。
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