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.
2. Thakur V, Bishnoi A, Vinay K, Kumaran SM, Parsad D (2021). Vitiligo: Translational research and effective therapeutic strategies. Pigment Cell Melanoma Res, 34:814-826.
3. Al Abadie MS, Gawkrodger DJ (2021). Integrating neuronal involvement into the immune and genetic paradigm of vitiligo. Clin Exp Dermatol, 46:646-650.
4. Chen J, Li S, Li C (2021). Mechanisms of melanocyte death in vitiligo. Med Res Rev, 41:1138-1166.
5. Kalluri R, LeBleu VS (2020). The biology, function, and biomedical applications of exosomes. Science, 7;367(6478):eaau6977.
6. Tavasolian F, Hosseini AZ, Rashidi M, et al (2021). The Impact of Immune Cell-derived Exosomes on Immune Response Initiation and Immune System Function. Curr Pharm Des, 27:197-205.
7. Barile L, Vassalli G (2017). Exosomes: Therapy delivery tools and biomarkers of diseases. Pharmacol Ther, 174:63-78.
8. Bae IS, Kim SH (2021). Milk Exosome-Derived MicroRNA-2478 Suppresses Melanogenesis through the Akt-GSK3β Pathway. Cells, 10(11):2848.
9. Melnik BC, John SM (2020). MicroRNA-21-Enriched Exosomes as Epigenetic Regulators in Melanomagenesis and Melanoma Progression: The Impact of Western Lifestyle Factors. Cancers (Basel), 29;12(8):2111.
10. Wong PM, Yang L, Yang L, et al (2020). New insight into the role of exosomes in vitiligo. Autoimmun Rev, 19:102664.
11. Takano K, Hachiya A, Murase D, et al (2020). Quantitative changes in the secretion of exosomes from keratinocytes homeostatically regulate skin pigmentation in a paracrine manner. J Dermatol, 47:265-276.
12. Jin S, Chen L, Xu Z, Xing X, Zhang C, Xiang L (2020). 585 nm light-emitting diodes inhibit melanogenesis through upregulating H19/miR-675 axis in LEDs-irradiated keratinocytes by paracrine effect. J Dermatol Sci, 98:102-108.
13. Tulkens J, De Wever O, Hendrix A (2020). Analyzing bacterial extracellular vesicles in human body fluids by orthogonal biophysical separation and biochemical characterization. Nat Protoc, 15:40-67.
14. Chen L, Heikkinen L, Wang C, Yang Y, Sun H, Wong G (2019). Trends in the development of miRNA bioinformatics tools. Brief Bioinform, 20:1836-1852.
15. Aguennouz M, Guarneri F, Oteri R, Polito F, Giuffrida R, Cannavò SP (2021). Serum levels of miRNA-21-5p in vitiligo patients and effects of miRNA-21-5p on SOX5, beta-catenin, CDK2 and MITF protein expression in normal human melanocytes. J Dermatol Sci, 101:22-29.
16. Shang Z, Li H (2017). Altered expression of four miRNA (miR-1238-3p, miR-202-3p, miR-630 and miR-766-3p) and their potential targets in peripheral blood from vitiligo patients. J Dermatol, 44:1138-1144.
17. Hushcha Y, Blo I, Oton-Gonzalez L, Mauro GD, Martini F, Tognon M, Mattei M (2021). microRNAs in the Regulation of Melanogenesis. Int J Mol Sci, 22.
18. Huo J, Liu T, Li F, Song X, Hou X (2021). MicroRNA‑21‑5p protects melanocytes via targeting STAT3 and modulating Treg/Teff balance to alleviate vitiligo. Mol Med Rep, 23 (1):51.
19. Seneschal J, Boniface K, D'Arino A, Picardo M (2021). An update on Vitiligo pathogenesis. Pigment Cell Melanoma Res, 34:236-243.
20. Le L, Sirés-Campos J, Raposo G, Delevoye C, Marks MS (2021). Melanosome Biogenesis in the Pigmentation of Mammalian Skin. Integr Comp Biol, 61:1517-1545.
21. Niu C, Aisa HA (2017). Upregulation of Melanogenesis and Tyrosinase Activity: Potential Agents for Vitiligo. Molecules, 22(8):1303.
22. Zhang J, Yu R, Guo X, et al (2021). Identification of TYR, TYRP1, DCT and LARP7 as related biomarkers and immune infiltration characteristics of vitiligo via comprehensive strategies. Bioengineered, 12:2214-2227.
23. Yang L, Wei Y, Sun Y, et al (2015). Interferon-gamma Inhibits Melanogenesis and Induces Apoptosis in Melanocytes: A Pivotal Role of CD8+ Cytotoxic T Lymphocytes in Vitiligo. Acta Derm Venereol, 95:664-70.
24. Liu Y, Xue L, Gao H, et al (2019). Exosomal miRNA derived from keratinocytes regulates pigmentation in melanocytes. J Dermatol Sci, 93:159-167.
25. Wang XY, Guan XH, Yu ZP, et al (2021). Human amniotic stem cells-derived exosmal miR-181a-5p and miR-199a inhibit melanogenesis and promote melanosome degradation in skin hyperpigmentation, respectively. Stem Cell Res Ther, 12:501.
26. Zhang Z, Yang X, Liu O, et al (2021). Differentially expressed microRNAs in peripheral blood mononuclear cells of non-segmental vitiligo and their clinical significance. J Clin Lab Anal, 35:e23648.
27. Zhang L, Cheng F, He R, Chen H, Liu Y, Sun J (2014). Inhibition of SATB1 by shRNA suppresses the proliferation of cutaneous malignant melanoma. Cancer Biother Radiopharm, 29:77-82.
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Issue | Vol 51 No 12 (2022) | |
Section | Original Article(s) | |
DOI | https://doi.org/10.18502/ijph.v51i12.11461 | |
Keywords | ||
Vitiligo Exosome MIRN21 microRNA Human Melanogenesis SATB1 protein |
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