Bone marrow mesenchymal stem cell-derived exosomes HADH alleviate vitiligo by activating the Nrf2/HO-1 pathway.

BACKGROUND

Vitiligo is a chronic skin disorder that significantly impairs patients' quality of life. Exosomes (Exos) have been reported to hold therapeutic promise for vitiligo. This study aimed to investigate the molecular mechanism by which bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) ameliorate vitiligo.

METHODS

In vitro vitiligo cell model was established by hydrogen peroxide (H2O2)-induced melanocytes. A mouse model of vitiligo was also established. Immunofluorescence, cell counting kit-8, 2',7'-dichlorofluorescein diacetate, enzyme linked immunosorbent assay, flow cytometry, real-time quantitative PCR, western blotting, hematoxylin-eosin, Masson-Fontana, and immunohistochemistry staining experiments were elucidated to explore the molecular mechanism of BMSC-Exos in relieving vitiligo.

RESULTS

H2O2 treatment reduce the cell viability, superoxide dismutase and catalase activities, and promote reactive oxygen species production, pyroptosis, the expression of NLRP3, ASC, IL-1β and IL-18 proteins in melanocytes. BMSC-Exos treatment effectively counteracted these detrimental effects. Knockdown of exosomal HADH derived from BMSC enhanced H2O2-induced oxidative stress and pyroptosis in melanocytes. Mechanistically, BMSC-Exos attenuated H2O2-induced oxidative stress and pyroptosis by mediating HADH delivery to activate the Nrf2/HO-1 pathway. Moreover, these results were further confirmed by experiments in a mouse model of vitiligo.

CONCLUSION

BMSC-Exos can alleviate vitiligo by delivering HADH to activate the Nrf2/HO-1 pathway. This study provides insights for exploring new treatments for vitiligo.