Transcription factors and stress response gene alterations in human keratinocytes following Solar Simulated Ultra Violet Radiation

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.

More Than Skin Deep: Autophagy Is Vital for Skin Barrier Function

“…Sun-generated UVR is a mixture of UVA and UVB ( 185 ). Upon exposure to UVR, basal autophagy increases in keratinocytes ( 28 ) and causes epidermal thickening or hyperkeratosis ( 28 ).…”

“…UVA (long wavelength) irradiation penetrates the dermis, and its exposure induces autophagy to remove p62-associated protein aggregates in keratinocytes and melanocytes ( 5 , 61 , 197 , 198 ). Chronic UVA exposure causes apoptosis of epidermal and dermal cells, photoaging, and skin pathogenesis, depending upon the presence of melanin ( 28 , 185 ). Luteolin (3, 4, 5, 7-tetrahydroxyflavone), a flavonoid showing anti-cancer properties, has recently been shown to decrease UVA-induced autophagy in human skin fibroblasts by scavenging ROS ( 95 , 191 ).…”

Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies

“…Two earliest identified transcription factors activated in response to UV radiation are activating protein 1/2 (AP-1/2) and nuclear factor kappa B (NF-κB). However, nuclear factor of activated T cells (NFAT), signal transducers and activators of transcription (STATs), and cellular tumor antigen p53 (TP53) may also take part in the UV response [ 8 , 47 , 50 , 51 , 52 ]. TP53 also works as an important factor that regulate chromatin accessibility allowing relaxation of the chromatin upon UV damage [ 53 ].…”

Autophagy: Multiple Mechanisms to Protect Skin from Ultraviolet Radiation-Driven Photoaging

“…Solar UV exposure is a crucial part of environmental stress that affects skin tissue damage. Exposure to solar UV radiation induces ROS to activate some cell surface receptors, e.g., epidermal growth factor receptor (EGFR) and tumor necrosis factor receptor (TNFR), and to initiate cell survival or apoptosis-associated signaling cascades [63,64]. Solar UV radiation activates one of the serine/threonine protein kinase family proteins and is associated with cellular signaling, i.e., the mitogen-activated protein kinase (MAPK) pathway.…”