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

Bustamante Pineda, Mariona; Hernandez-Ferrer, Carles, 1987-; Tewari, Angela; Sarria-Trujillo, Yaris; Harrison, Graham I.; Puigdecanet Riubugent, Eulàlia; Nonell Mazelon, Lara, 1972-; Kang, Wenjing; Friedländer, Marc R.; Estivill, Xavier, 1955-; González, Juan Ramón; Nieuwenhuijsen, Mark J.; Young, Antony R.

doi:http://dx.doi.org/10.1111/bjd.18527

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

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Bustamante M, Hernandez-Ferrer C, Tewari A, Sarria Y, Harrison GI, Puigdecanet E et al. Dose and time effects of solar-simulated ultraviolet radiation on the in vivo human skin transcriptome. Br J Dermatol. 2020; 182(6):1458-68. DOI: 10.1111/bjd.18527

Abstract

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.