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Accumulation studies have found that adipose-derived stem cell (ADSC) exosomes have anti-oxidant and anti-inflammatory characteristics. The current study verified their therapeutic potential to elucidate mechanisms of ADSC exosome actions in ultraviolet B (UVB) light-induced skin injury. Exosomes were isolated from ADSCs and hypoxic pretreated ADSCs. Next-generation sequencing (NGS) was applied to characterize differential mRNA expression. A UV-induced mice skin injury model was generated to investigate therapeutic effects regarding the exosomes via immunofluorescence and ELISA analysis. Regulatory mechanisms were illustrated using luciferase report analysis and in vitro experiments. The results demonstrated that exosomes from hypoxic pretreated ADSCs (HExos) inhibited UVB light-induced vascular injury by reversing reactive oxygen species, inflammatory factor expression and excessive collagen degradation. NGS showed that HExos inhibits UV-induced skin damage via GLRX5 delivery, while GLRX5 downregulation inhibited the therapeutic effect of HExos on UV-induced skin damage. GLRX5 upregulation increased the protective Exo effect on UV-induced skin and EPC damage by inhibiting ferroptosis, inflammatory cytokine expression and excessive collagen degradation. Therefore, the data indicate that HExos attenuate UV light-induced skin injury via GLRX5 delivery and ferroptosis inhibition., (© 2023. The Author(s), under exclusive licence to European Photochemistry Association, European Society for Photobiology.)

Background: An increasing number of studies have reported that exosomes from adipose-derived stem cells (ADSCs) have antioxidant and anti-inflammatory properties. In the present study, we aimed at elucidating the potential therapeutic mechanism underlying ADSC exosomes in ultraviolet B-light (UVB)-induced skin injury., Methods: We isolated the exosomes from ADSCs and hypoxia-pretreated ADSCs. High-throughput sequencing was applied to identify differential circRNA expression. Then, a UV-induced murine skin injury model was constructed and the therapeutic effect of exosomes was determined using immunofluorescence and ELISA. The regulatory mechanism was demonstrated using luciferase reporter analysis and an in vitro experiment., Results: Exosomes from hypoxia-pretreated ADSCs inhibited UVB light-induced vascular injury by reversing ROS and inflammatory factor expression. High-throughput sequencing showed that exosomes from hypoxia-pretreated ADSCs (HExo) improved UV-induced skin damage via delivery of circ-Ash1l. Downregulation of circ-Ash1l inhibited the therapeutic effect of HExo on UV-induced skin damage. It was further shown that GPX4 and miR-700-5p were circ-Ash1l downstream targets. MiR-700-5p overexpression or GPX4 downregulation inhibited the circ-Ash1l protective effects of UV-induced endothelial progenitor cell (EPC) damage., Conclusion: Thus, exosomes from hypoxia-pretreated ADSCs attenuated UV light-induced skin injury via circ-Ash1l delivery and ferroptosis inhibition., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)