Abstract
Ultraviolet radiation (UVR) from sunlight is the major effector for skin aging and carcinogenesis. However, genes and pathways altered by solar-simulated UVR (ssUVR), a mixture of UVA and UVB, are not well characterized. Here we report global changes in gene expression as well as associated pathways and upstream transcription factors in human keratinocytes exposed to ssUVR. Human HaCaT keratinocytes were exposed to either a single dose or 5 repetitive doses of ssUVR. Comprehensive analyses of gene expression profiles as well as functional annotation were performed at 24 hours post irradiation. Our results revealed that ssUVR modulated genes with diverse cellular functions changed in a dose-dependent manner. Gene expression in cells exposed to a single dose of ssUVR differed significantly from those that underwent repetitive exposures. While single ssUVR caused a significant inhibition in genes involved in cell cycle progression, especially G2/M checkpoint and mitotic regulation, repetitive ssUVR led to extensive changes in genes related to cell signaling and metabolism. We have also identified a panel of ssUVR target genes that exhibited persistent changes in gene expression even at 1 week after irradiation. These results revealed a complex network of transcriptional regulators and pathways that orchestrate the cellular response to ssUVR.
Highlights
Solar ultraviolet radiation (UVR) is one of the most impactful environmental factors affecting human skin and leads to an array of photo damage endpoints, including sunburn, erythema, edema, immune suppression, as well as skin cancers[1]
To mimic human skin repetitively exposed to solar-simulated UVR (ssUVR), cells were exposed to 5 repetitive doses of ssUVR at 3, 6, 12 J/cm[2] and were collected at 24 hours post irradiation
To examine the persistence of gene expression changes, cells were exposed to 5 repetitive doses of ssUVR at 12 J/cm[2], and were collected at 1 week after the last irradiation
Summary
Solar ultraviolet radiation (UVR) is one of the most impactful environmental factors affecting human skin and leads to an array of photo damage endpoints, including sunburn, erythema, edema, immune suppression, as well as skin cancers[1]. The ozone layer effectively blocks most solar radiation that has wavelength less than 290 nm, so that the UVR reaching the skin surface is a mixture of 5–10% UVB (290–320 nm) and 90–95% of UVA (320–400 nm). Both UVA and UVB are able to induce DNA damage in mammalian cells. DNA-damage induced signaling cascades are activated; DNA replication and transcription are temporarily stalled at the sites of damage; and chromosome segregation is paused at cell cycle checkpoints These events lead to dynamic transcriptional changes that subsequently contribute to a series of divergent cellular UV responses, including DNA damage repair, cell cycle arrest, and apoptosis[10]. Only a limited number of genes were analyzed in these studies
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