Identification of the role of wnt/β-catenin pathway through integrated analyses and in vivo experiments in vitiligo
Zhao SJ, Jia H, Xu XL, Bu WB, Zhang Q, Chen X, Ji J, Sun JF (2021)
Publication Type: Journal article
Publication year: 2021
Journal
Book Volume: 14
Pages Range: 1089-1103
DOI: 10.2147/CCID.S319061
Abstract
Purpose: Vitiligo is an acquired depigmentation skin disease, which affects an average of 1% of the world’s population. The purpose of this study is to identify the key genes and pathways responsible for vitiligo and find new therapeutic targets. Methods: The datasets GSE65127, GSE53146, and GSE75819 were downloaded from the Gene Expression Omnibus (GEO) database. R language was used to identify the differentially expressed genes (DEGs) between lesional skin of vitiligo and non-lesional skin. Next, the key pathways were obtained by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The protein–protein interaction (PPI) networks were conducted by STRING database and Cytoscape software. Subsequently, module analysis was performed by Cytoscape. Among these results, the Wnt/β-catenin pathway and melanogenesis pathway caught our attention. The expression level of β-catenin, microphthalmia-associated transcription factor (MITF) and tyrosinase (TYR) was detected by immunofluorescence in vitiligo lesions and healthy skin. Moreover, zebrafish was treated with XAV-939, an inhibitor of the Wnt/β-catenin pathway. After that, the area of melanin granules as a percentage of the head area was measured. The mRNA expression of β-catenin, lymphoid-enhancing factor 1(lef1), tyr and mitf were detected by q-PCR (quantitative polymerase chain reaction) in zebrafish (Danio rerio). Results: A total of 2442 DEGs were identified, including 1068 upregulated and 1374 downregulated DEGs. The key pathways were identified by GO and KEGG analyses, such as “NOD-like receptor signaling pathway”, “Wnt signaling pathway”, “Melanogenesis”, “mTOR signaling pathway”, “PI3K-Akt signaling pathway”, “Calcium signaling pathway” and “Rap1 signaling pathway”. The immunofluorescence results showed that the level of βcatenin, MITF and TYR was significantly downregulated in vitiligo lesional skin. In zebrafish, the mean percentage area of melanin granules and the expression of β-catenin, lef1, tyr and mitf were decreased after treated with XAV-939. Conclusion: The present study identified key genes and signaling pathways associated with the pathophysiology of vitiligo. Among them, the Wnt/β-catenin pathway played an essential role in pigmentation and could be a breakthrough point in vitiligo treatment.
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APA:
Zhao, S.-J., Jia, H., Xu, X.-L., Bu, W.-B., Zhang, Q., Chen, X.,... Sun, J.-F. (2021). Identification of the role of wnt/β-catenin pathway through integrated analyses and in vivo experiments in vitiligo. Clinical, Cosmetic and Investigational Dermatology, 14, 1089-1103. https://dx.doi.org/10.2147/CCID.S319061
MLA:
Zhao, Si-Jia, et al. "Identification of the role of wnt/β-catenin pathway through integrated analyses and in vivo experiments in vitiligo." Clinical, Cosmetic and Investigational Dermatology 14 (2021): 1089-1103.
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