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

  • Mech Ageing Dev. 2026 Aug:232:112194. doi: 10.1016/j.mad.2026.112194.
Tingting Wang  1 ,  Nan Huang  2 ,  Xiaofang Zhang  3 ,  Ting Yan  4
Affiliations
  • 1. Department of Dermatovenereology, West China Hospital, Sichuan University, Chengdu, China; Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology (CIII), Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China. Electronic address: [email protected].
  • 2. Department of Dermatovenereology, West China Hospital, Sichuan University, Chengdu, China; Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology (CIII), Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
  • 3. Department of Dermatology, Mianyang 404 Hospital, Mianyang, Sichuan 621000, China.
  • 4. Sichuan Botanee Biotechnology Co., Ltd, Chengdu, Sichuan 610000, China.
PMID: 42155870 DOI: 10.1016/j.mad.2026.112194
Abstract

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.

Keywords
Pro-Xylane; SGK1; Skin senescence; UVB; Ubiquitination.
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