Pro-Xylane alleviates ultraviolet-induced skin senescence through SGK1-mediated p21 ubiquitination and subcellular translocation.

BACKGROUND Ultraviolet B (UVB) radiation causes skin damage, leading to aging and inflammatory responses. Pro-Xylane, a plant-derived compound, has been proposed for its potential protective effects against UVB-induced skin damage. However, its molecular mechanisms, particularly regarding cellular senescence, remain unclear.

METHODS HaCaT cells were exposed to UVB radiation and treated with Pro-Xylane. The effects on cell viability, apoptosis, reactive oxygen species (ROS) production, senescence markers, and collagen expression were assessed via CCK-8, TUNEL staining, DCFH-DA, and immunofluorescence assays. GEO datasets identified SGK1 as a key target. The p21 ubiquitination and subcellular localization were analyzed via immunoprecipitation and Western blot. In vivo experiments were conducted using UVB-irradiated rats to confirm the therapeutic effects of Pro-Xylane on skin regeneration.

RESULTS Pro-Xylane improved cell viability and inhibited ROS production in UVB-exposed HaCaT cells. Pro-Xylane decreased β-galactosidase expression and reversed UVB-induced upregulation of p21. SGK1 was identified as a key mediator in the protective effects. Pro-Xylane promoted mitochondrial function, and reduced oxidative stress. Mechanistically, Pro-Xylane promoted p21 ubiquitination (K141) and cytoplasmic retention, counteracting UVB-induced nuclear p21 accumulation.

CONCLUSION Pro-Xylane effectively mitigated UVB-induced skin senescence and damage through SGK1-mediated p21 ubiquitination and subcellular translocation, making it a promising candidate for skin repair and anti-aging treatments.