Abstract
Skin photodamage affects appearance and increases cancer risk, yet existing treatments are inadequate. Our prior data indicate that skin-derived precursors (SKPs) protect against photodamage via exosome-mediated signaling, though the mechanism is unclear. Exosomes are stable stem cell regulators, but SKPs-derived exosomes (SKPs-Exo) are underexplored in photodamage. To assess SKPs-Exo’s therapeutic potential and mechanism in UVB-induced skin damage using mouse and 3D skin models. SKPs-Exo were isolated via ultracentrifugation and characterized by TEM, NTA, and WB. UVB-irradiated mice and 3D skin models received varying SKPs-Exo doses. We evaluated skin damage, apoptosis (TUNEL), oxidative stress (ROS, MDA, GSH, SOD), inflammation (IL-1β, IL-6, TNF-α), and Nrf2, HO-1, BACH1, and NF-κB expression. SKPs-Exo (30–200 nm) expressed CD9, CD63, and TSG101. UVB-induced damage, apoptosis, oxidative stress, and inflammation were dose-dependently reduced by SKPs-Exo, which restored antioxidants, suppressed inflammation, and modulated Nrf2/HO-1 and BACH1/NF-κB pathways (P < 0.05 or P < 0.01). SKPs-Exo alleviate UVB-induced skin damage by reducing apoptosis, oxidative stress and inflammation, likely via activating the Nrf2/HO-1 pathway and suppressing the BACH1/NF-κB pathway, providing a potential therapeutic direction for skin photodamage.
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Acknowledgements
We extend our heartfelt appreciation to the Clinical Medical Research Center of the Affiliated Hospital of Southwest Medical University, the Experimental Animal Center of Southwest Medical University, and the Laboratory of Neurobiology for their invaluable support in our research endeavors. Additionally, we are deeply grateful to EditSprings for their expert editorial assistance, which has markedly enhanced the quality of this manuscript.
Funding
The study was supported by the Sichuan Province Natural Science Youth Foundation (2026NSFSC1522), the Science༆Technology Bureau of Luzhou, Sichuan Province, China (Grant no: 2023JYJ039) and the Luzhou Municipal People’s Government-Southwest Medical University Science and Technology Section Strategic Cooperation Project (2023ZD009).
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Xian, K., Liu, L., Huang, X. et al. Protective effects of skin-derived precursor cell exosomes against UVB-induced skin photodamage. Sci Rep (2026). https://doi.org/10.1038/s41598-026-48604-1
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DOI: https://doi.org/10.1038/s41598-026-48604-1


