Abstract
Despite their preponderance amongst the ultraviolet (UV) range received on Earth, the biological impacts of longwave UVA1 rays (340–400 nm) upon human skin have not been investigated so thoroughly. Nevertheless, recent studies have proven their harmful effects and involvement in carcinogenesis and immunosuppression. In this work, an in vitro reconstructed human skin model was used for exploring the effects of UVA1 at molecular, cellular and tissue levels. A biological impact of UVA1 throughout the whole reconstructed skin structure could be evidenced, from morphology to gene expression analysis. UVA1 induced immediate injuries such as generation of reactive oxygen species and thymine dimers DNA damage, accumulating preferentially in dermal fibroblasts and basal keratinocytes, followed by significant cellular alterations, such as fibroblast apoptosis and lipid peroxidation. The full genome transcriptomic study showed a clear UVA1 molecular signature with the modulation of expression of 461 and 480 genes in epidermal keratinocytes and dermal fibroblasts, respectively (fold change> = 1.5 and adjusted p value<0.001). Functional enrichment analysis using GO, KEGG pathways and bibliographic analysis revealed a real stress with up-regulation of genes encoding heat shock proteins or involved in oxidative stress response. UVA1 also affected a wide panel of pathways and functions including cancer, proliferation, apoptosis and development, extracellular matrix and metabolism of lipids and glucose. Strikingly, one quarter of modulated genes was related to innate immunity: genes involved in inflammation were strongly up-regulated while genes involved in antiviral defense were severely down-regulated. These transcriptomic data were confirmed in dose-response and time course experiments using quantitative PCR and protein quantification. Links between the evidenced UVA1-induced impacts and clinical consequences of UVA1 exposure such as photo-aging, photo-immunosuppression and cancer are discussed. These early molecular events support the contribution of UVA1 to long term harmful consequences of UV exposure and underline the need of an adequate UVA1 photoprotection.
Highlights
Human skin is the largest body organ
To appreciate the impact of UVA1 wavelengths upon human reconstructed skin and based upon our previous studies on UVA exposure, we determined the UVA1 Biologically Efficient Dose (BED), i.e. the minimal dose necessary to induce morphological changes without destroying the tissue using histology and vimentin immunostaining to assess the viability of dermal fibroblasts and epidermal keratinocytes [16] (Figure 1)
We showed that effects of UVA1 and total UVA spectra were qualitatively similar, at quite equivalent doses (40 J/cm2 UVA1 and 35–40J/cm2 total UVA), with at these doses the clear disappearance of superficial dermal fibroblasts 48 h post exposure
Summary
Human skin is the largest body organ. Solar ultraviolet (UV) rays constitute one of the external factors to which human skin is acutely as well as chronically exposed and can induce biological and clinical damage, such as sunburn, immunosuppression, photocarcinogenesis and photoaging. UV rays that can reach the earth surface are a combination of UVB and UVA wavelengths. UVA rays are mostly responsible for the generation of reactive oxygen species (ROS) leading to oxidative stress. UVA can reach the deep dermis and induce dermal damage. In the long term UVA are mostly involved in skin photoaging. Both UVA and UVB have been shown to be responsible for pigmentation, photoimmunosuppression and photocarcinogenesis [2]
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