Epigenetic downregulation of MAPKAPK2 exacerbates oxidative stress-induced damage in vitiligo melanocyte cell line model.

Background and objective: Vitiligo is an acquired depigmentation disorder caused by melanocyte dysfunction or loss. Oxidative stress is widely considered a key driver to its pathogenesis. Mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK2) is implicated in oxidative stress responses, although its role in vitiligo remains uncertain. This study intended to investigate whether epigenetic downregulation of MAPKAPK2 aggravates oxidative stress-induced damage in vitiligo melanocytes. Methods: Human melanocyte lines (PIG1 and PIG3V) were used to model normal and vitiligo conditions. The effects of oxidative stress, DNA demethylation (5-aza-DC), and MAPKAPK2 overexpression were assessed using qRT-PCR, Western blot, ELISA, comet assay, TUNEL, and CCK-8. Pharmacological inhibition of MK2 was employed to evaluate the functional requirement of MAPKAPK2 kinase activity, and key antioxidant pathways, including Nrf2 signaling, were investigated. Results: MAPKAPK2 expression was notably downregulated in PIG3V cells compared with PIG1 cells ( Conclusion: Epigenetic silencing of MAPKAPK2 aggravates oxidative damage in vitiligo melanocytes, potentially by attenuating Nrf2-associated antioxidant responses. These findings identify MAPKAPK2 as a functionally relevant and targetable factor in the oxidative pathology of vitiligo.