Knockdown of Simulated-Solar-Radiation-Sensitive miR-205-5p Does Not Induce Progression of Cutaneous Squamous Cell Carcinoma In Vitro
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PROVIDER: S-EPMC10671527 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
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Project description:Long-term exposure of human skin to ultraviolet radiation (UVR) in sunlight negatively impacts its appearance and function with photoaged skin having a characteristic leathery, rough appearance, with deep wrinkles. These clinical features of photodamage are thought to result from UVR-induced remodelling of the dermal extracellular matrix, particularly the elastic fibre system. There are few in vivo human data on the impact of acute UVR exposure on this fibre system and particularly solar-simulated radiation (SSR)-mediated effects. We examined the differential effect of broadband UVB and SSR on the human dermal elastic fibre system, and specifically the microfibrillar components fibrillin-1, fibulin-2 and fibulin-5. Healthy white Caucasian adults (skin type II-III) were recruited and irradiated with 3× their minimal erythema dose of broadband UVB (n = 6) or SSR (n = 6) on photoprotected buttock skin. Punch biopsies were taken 24 h after irradiation and from unirradiated control skin. Overall, histological assessment of elastic fibres revealed significantly less elastic fibre staining in broadband UVB (P = 0.004) or SSR (P = 0.04) irradiated skin compared to unirradiated control skin. Significantly less staining of fibrillin-1-positive microfibrils was also observed in the papillary dermis of UVB irradiated skin (P = 0.02) but not skin exposed to SSR. Conversely, immunohistochemistry for fibulin-5-positive microfibrils revealed significantly less expression in skin exposed to SSR (P = 0.04) but not to broadband UVB. There was no significant change in fibulin-2-positive microfibrils following either broadband UVB or SSR irradiation. Thus, broadband UVB and SSR mediate differential effects on individual components of the dermal elastic fibre network in human skin. Further human studies are required to explore the mechanisms underlying these findings and the impact of potential photoprotective agents.
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Project description:Despite widespread use of sunscreens that minimize erythema by blocking ultraviolet B (UVB) radiation, incidence rates of melanoma continue to rise. In considering this disparity between intervention and disease prevalence, we investigated the in vivo transcriptome of human skin treated with sunscreen and solar-simulated radiation (ssR). A focal skin area of healthy participants was exposed to ssR at 1 minimal erythema dose (MED), 0.1 MED or 100 J/m2 with or without prior application of sunscreen, or to non-UVB-spectrum of ssR (solar-simulated UVA/visible/infrared radiation: ssA). Skin biopsies were analyzed using expression microarrays. Ninety-eight microarrays from 14 healthy human volunteers were analyzed. Focal skin areas of all 14 volunteers were exposed to 0 J/m2, 100 J/m2, 1 minimal erythema dose (MED), and 0.1 MED of solar-simulated radiation (ssR). Eight of the 14 volunteers (Group 1) were also exposed to ssA (ssR minus UVB) that were generated by removing UVB from 0 J/m2, 100 J/m2, 1 minimal erythema dose (MED), and 0.1 MED of ssR. Additionally, 6 of the 14 volunteers (Group 2) were treated with sunscreen of sun protection factor (SPF) 15, and exposed to 0 J/m2, 100 J/m2, 1 minimal erythema dose (MED), and 0.1 MED of ssR. Biopsy was taken 24 hours after exposure from each focal skin area for RNA extraction.
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Project description: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 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 lead 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.
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