These data demonstrate that GR protects human melanocytes from H2O2‑induced oxidative damage via the Nrf2‑dependent induction of HO‑1, providing evidence for the application of GR in the treatment of vitiligo.
These data demonstrated that external stimuli (eg, oxidative stress) may trigger autocrine HMGB1 translocation and release by melanocytes, suppressing the expression of Nrf2 and downstream antioxidant genes to induce melanocyte apoptosis, and thereby participate in the pathological process of vitiligo.
Therefore, our data demonstrated that dysregulated autophagy owing to the impairment of Nrf2-p62 pathway increase the sensitivity of vitiligo melanocytes to oxidative stress, thus promote the development of vitiligo.
Therefore, impaired PI3K activation in keratinocytes in depigmented epidermis of vitiligo patients are vulnerable to apoptosis caused by ROS-generating chemicals due to reduced Nrf2 activation.
Taken together, our results show that simvastatin protects human melanocytes from H<sub>2</sub>O<sub>2</sub>-induced oxidative stress by activating Nrf2, thus supporting simvastatin as a potential therapeutic agent for vitiligo.
Depigmented epidermis of vitiligo patients also showed lower levels of Nrf2 and phospho-PI3K but higher levels of ROS, TNF-ɑ, IL-1ɑ, and ROS with more TUNEL-positive cells.
Theories including reactive oxygen species model, Nrf2-antioxidant response element (ARE) pathway, WNT pathway, tyrosinase activity, biochemical, molecular, and cellular alterations have been hypothesized to explain vitiligo pathogenesis.
These findings indicate that the C allele of rs35652124 located in the promoter region of Nrf2 gene is associated with protective effect on vitiligo in a Han Chinese population.