Molecular Responses of Human Skin to Single and Repeated Low Dose Solar Simulated UVR Exposure

Solar ultraviolet radiation (UVR) significantly influences human health, yet the early molecular effects of everyday low dose exposure remain poorly understood. This study investigated acute molecular events in human skin following single and repeated low dose UVR exposure, providing insights into early regulatory networks underlying cutaneous UVR responses. Healthy volunteers (n=6, 5 female, age 28-65 years, skin type II-III) received low dose solar simulated UVR to upper buttock skin on 3 consecutive days, with biopsies collected 30 minutes, 3 hours and 24 hours following the 1st exposure, 24 hours following the 3rd exposure, and from unexposed skin. Biopsies were assessed by immunostaining and RNA-sequencing. Whereas the single exposure induced few transcriptomic changes, repeated UVR exposure elicited a robust response with 1,498 differentially expressed genes vs unexposed skin. This included numerous long non-coding RNAs and showed pathway enrichment related to cell cycle activation, inflammation, and interferon signalling. Accompanying this was activation of upstream regulators including interferons, growth factors and pro-inflammatory molecules. Immunostaining suggested an apparent (non-significant) increase in epidermal cell proliferation and immune infiltration after 3 low dose UVR challenges. Findings demonstrate that even brief repeated UVR exposures can induce cumulative effects, evoking molecular responses relevant to skin physiology.