Exosomal miR-493-3p Promote the Secretion of CXCL10 by Suppressing Keratinocyte Autophagy in Vitiligo.

BACKGROUND: Vitiligo is a dermatological disorder characterized by the destruction of melanocytes, resulting from a complex interplay of genetic, immune and environmental factors. Recent studies have highlighted the involvement of keratinocytes in the pathogenesis of vitiligo; however, the precise mechanisms underlying this process remain to be fully elucidated. This study aimed to elucidate the specific role of keratinocytes in vitiligo pathogenesis, investigate autophagic changes in lesional keratinocytes, validate miR-493-3p's regulatory effect on keratinocyte autophagy. METHODS: Initially, the role of keratinocytes in vitiligo lesions were evaluated by reanalyzing single-cell transcriptome data from public databases. Subsequently, a comprehensive analysis of differentially expressed genes was conducted, focusing particularly on changes in the autophagy within keratinocytes. Finally, in vitro studies, including Western Blotting, ELISA, and immunofluorescence assays, were utilized to validate the effects of miR-493-3p on the autophagy, which are implicated in the secretory dysfunction of keratinocytes. RESULTS: Our study revealed a reduction in the number of keratinocytes in vitiligo lesions, and autophagy was significantly enriched in both WGCNA and KEGG analyses. Additionally, we demonstrated that miR-493-3p directly inhibits the expression of LC3, leading to a decrease in autophagy. Ultimately, we confirmed that autophagy dysfunction results in an increase in CXCL10 levels in keratinocytes, which may be associated with immune-mediated damage to melanocytes. CONCLUSION: Our research illustrates the role of keratinocytes in vitiligo and clarifies how miR-493-3p induces secretion dysfunction in keratinocytes by modulating autophagy.