Dose and time effects of solar‐simulated ultraviolet radiation on the in vivo human skin transcriptome

Abstract

Summary Background Terrestrial ultraviolet (UV) radiation causes erythema, oxidative stress, DNA mutations and skin cancer. Skin can adapt to these adverse effects by DNA repair, apoptosis, keratinization and tanning. Objectives To investigate the transcriptional response to fluorescent solar‐simulated radiation (FSSR) in sun‐sensitive human skin in vivo. Methods Seven healthy male volunteers were exposed to 0, 3 and 6 standard erythemal doses (SED). Skin biopsies were taken at 6 h and 24 h after exposure. Gene and microRNA expression were quantified with next generation sequencing. A set of candidate genes was validated by quantitative polymerase chain reaction (qPCR); and wavelength dependence was examined in other volunteers through microarrays. Results The number of differentially expressed genes increased with FSSR dose and decreased between 6 and 24 h. Six hours after 6 SED, 4071 genes were differentially expressed, but only 16 genes were affected at 24 h after 3 SED. Genes for apoptosis and keratinization were prominent at 6 h, whereas inflammation and immunoregulation genes were predominant at 24 h. Validation by qPCR confirmed the altered expression of nine genes detected under all conditions; genes related to DNA repair and apoptosis; immunity and inflammation; pigmentation; and vitamin D synthesis. In general, candidate genes also responded to UVA1 (340–400 nm) and/or UVB (300 nm), but with variations in wavelength dependence and peak expression time. Only four microRNAs were differentially expressed by FSSR. Conclusions The UV radiation doses of this acute study are readily achieved daily during holidays in the sun, suggesting that the skin transcriptional profile of ‘typical’ holiday makers is markedly deregulated. What's already known about this topic? The skin's transcriptional profile underpins its adverse (i.e. inflammation) and adaptive molecular, cellular and clinical responses (i.e. tanning, hyperkeratosis) to solar ultraviolet radiation. Few studies have assessed microRNA and gene expression in vivo in humans, and there is a lack of information on dose, time and waveband effects. What does this study add? Acute doses of fluorescent solar‐simulated radiation (FSSR), of similar magnitude to those received daily in holiday situations, markedly altered the skin's transcriptional profiles. The number of differentially expressed genes was FSSR‐dose‐dependent, reached a peak at 6 h and returned to baseline at 24 h. The initial transcriptional response involved apoptosis and keratinization, followed by inflammation and immune modulation. In these conditions, microRNA expression was less affected than gene expression.

Environmental effects of stratospheric ozone depletion, UV radiation, and interactions with climate change: UNEP Environmental Effects Assessment Panel, Update 2020

“…Depending on the wavelength, dose, and frequency of exposure to UV radiation, adaptive (i.e., acquired) immune responses are often suppressed [ 103 , 104 ]. Exposure to UV radiation induces alterations to cutaneous cells, molecules [ 105 ], the transcriptome [ 106 ], and commensal bacteria [ 107 ], leading to the downstream activation of regulatory T and B cells. These exert their suppressive effects for sustained periods of time, both locally at the site of exposure to UV radiation and distantly at un-irradiated sites (Fig.…”

Insufficient Sun Exposure Has Become a Real Public Health Problem

“…Because the cutaneous production of vitamin D is dependent on solar UVB exposure, this vitamin (in fact a hormone) has commonly been assumed to account for all the beneficial effects of sunshine that have been suggested by ecologic studies (e.g., latitude gradients of some diseases). More recently, there has been greater awareness of the diversity of cutaneous mediators released in response to UVR, which also has a large effect on the skin transcriptome [ 5 , 6 ]. There is also evidence that solar UVR may affect the blood transcriptome [ 6 , 7 ], including genes for immunity.…”

The changing transcriptome in human skin following in vivo exposure to erythemal solar‐simulated ultraviolet radiation

“…In the analysis of time‐ and dose‐dependent transcriptional changes in human skin, two potentially important homeostatic responses were uncovered . The first was decreased expression of cytochrome P450 2R1 (CYP2R1) at 6 h and 24 h after exposure to erythemal FSSR, UVA1 and UVB.…”

“…The detailed and rigorous study by Bustamante et al . gives further insights into how sun‐sensitive skin responds acutely to erythemal sunlight . When buttock skin biopsies were taken 6 h after the exposure of seven sun‐sensitive individuals to approximately double an erythemal dose (six standard erythema doses) of fluorescent solar‐simulated radiation (FSSR), transcriptional changes in 4071 genes, i.e.…”

“…The production of UVR‐induced vitamin D metabolites also did not correlate with FSSR‐induced transcriptional changes. It had previously been reported that the concentration of 25(OH)D 3 in plasma continued to rise for 48 h after erythemal FSSR, while the transcriptional changes in blood cells were greater at 6 h and had returned to initial levels by 24 h. The same pattern of timing after FSSR exposure was exhibited in the skin as described in the present study . The second finding was reduced expression of many core pigment genes 6 h after exposure to FSSR, and thus a brake was being applied on the production of potentially toxic levels of pigment.…”