The antioxidant stress effect of granulin precursor in vitiligo

The imbalance of the skin redox system is regarded as a crucial factor contributing to the loss of melanocytes in vitiligo. However, it remains unclear whether alterations in signal transmission between melanocytes and other cells impact the homeostasis of the skin microenvironment. Hence, leveraging single-cell sequencing and microarray data, we investigated the role of cell-cell and ligand receptor interactions in the pathogenesis of vitiligo. We discovered that the granulin-sortilin 1 ligand-receptor serves as an essential bridge for communication between melanocytes and other skin cells in normal skin, yet it is significantly downregulated in vitiligo lesions. Enrichment analysis indicates that the activation of granulin-sortilin 1 ligand-receptor is closely associated with the regulation of oxidative stress. In vitro experiments have verified that progranulin, the protein encoded by the granulin gene, enhances the ability of melanocytes to resist cell death induced by reactive oxygen species and markedly upregulates the expression of nuclear factor erythroid 2-related factor 2 and Heme Oxygenase-1. Notably, this process can be impeded by the interaction inhibitor. Moreover, the expression of nuclear factor erythroid 2-related factor 2 might be linked to the transcription of transcription factor EB activated by progranulin. In conclusion, the granulin-sortilin 1 ligand-receptor can activate the intracellular antioxidant system to counteract melanocyte death. The impairment of the granulin-sortilin 1 ligand-receptor may be implicated in melanocyte loss in vitiligo.