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

Abstract

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.

Research progress of vitiligo repigmentation: from oxidative stress to autoimmunity

“…These exosomes create an inflammatory microenvironment, causing inflammation along with recruiting immune cells to clear stressed melanocytes. In their study, Zhang et al [25] reported that the patient-derived exosome miR-21-5p inhibited melanin production in melanocytes by targeting SATB1 in vitiligo. In addition, the downregulation of keratinocyte-derived exosome miR-200c inhibits melanin production in vitiligo lesions [26].…”

Exosomes: The emerging mechanisms and potential clinical applications in dermatology

“…MiR-493-3p-overexpressing keratinocyte induced melanocyte apoptosis and decreased melanin synthesis through inhibiting HNRNPU expression and increasing dopamine secretion (46). Circulating exosomes from vitiligo patients, containing miR-21-5p, inhibited melanin content, tyrosinase activity, and melanogenesis-related protein expression in melanocytes via inhibiting SATB1 expression (47). Moreover, Luo et al reported that exosomal hsa-miR-487b-3p in serum was significantly lower in vitiligo patients and positively correlated with the area of lesions in progressive vitiligo patients (14).…”

Exosomal miRNAs in autoimmune skin diseases

“…Several researches have yielded positive results that circulating exosomal miRNAs contribute to vitiligo's pathogenesis. Zhang et al (13) co-cultured circulating exosomes from vitiligo patients with the human melanocyte cell line PIG1. They observed the inhibition of melanogenesis, decreased tyrosinase activity, and altered expression of genes related to melanogenesis in melanocytes.…”