He Qiu, Qiang Ji, Ciqiong Chen, Jin Huang, Dongmei Wu
HDFs-EXO attenuate UVB-induced photoaging in association with reduced oxidative DNA damage and modulation of PGC-1α/Nrf2 signaling. These results support further investigation of HDFs-EXO as a cell-free approach for photoaging-related skin damage.
BACKGROUND: Aging, particularly photoaging induced by ultraviolet B (UVB) exposure, is characterized by oxidative DNA damage and extracellular matrix degradation. Exosomes are small vesicles secreted by cells and may mitigate oxidative stress and protect against photoaging. This study investigated the role of human dermal fibroblast-derived exosomes (HDFs-EXO) in alleviating UVB-induced photoaging and the underlying mechanisms.
METHODS: HDFs-EXO were isolated and characterized by size, morphology, and exosomal markers. HDFs received a single ultraviolet B (UVB) exposure followed immediately by HDFs-EXO treatment for 48 h. Cell viability, cell-cycle distribution, reactive oxygen species (ROS), matrix metalloproteinase-1 (MMP-1), type I collagen (COL-1), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and phosphorylated histone H2AX (γH2AX) were assessed. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling was investigated using PGC-1α knockdown.
RESULTS: HDFs-EXO enhanced cell viability, restored cell-cycle distribution, and reduced ROS levels in UVB-irradiated HDFs. They downregulated MMP-1 expression and upregulated COL-1, indicating a reduction in photoaging markers. Additionally, HDFs-EXO alleviated oxidative DNA damage, as evidenced by decreased 8-OHdG levels and γH2AX expression. HDFs-EXO altered the expression of PGC-1α/Nrf2-associated proteins. PGC-1α knockdown partially attenuated the protective effects of HDFs-EXO, supporting a contribution of PGC-1α-related signaling without establishing complete mediation or direct Nrf2 transcriptional activation.
CONCLUSION: HDFs-EXO attenuate UVB-induced photoaging in association with reduced oxidative DNA damage and modulation of PGC-1α/Nrf2 signaling. These results support further investigation of HDFs-EXO as a cell-free approach for photoaging-related skin damage.