Identification of the Role of Wnt/β-Catenin Pathway Through Integrated Analyses and in vivo Experiments in Vitiligo.

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 and were detected by q-PCR (quantitative polymerase chain reaction) in zebrafish ().

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 β-catenin, MITF and TYR was significantly downregulated in vitiligo lesional skin. In zebrafish, the mean percentage area of melanin granules and the expression of and 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.