Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Regulation of human skin pigmentation in situ by repetitive UV exposure - Molecular characterization of responses to UVA, UVB and SSR

ABSTRACT: To test the hypothesis that different mechanisms and/or factors might be involved in physiological pigmentary responses of the skin to different types of UV, we used whole human genome microarrays and immunohistochemical analyses to characterize human skin in situ to examine how melanocyte-specific proteins and paracrine melanogenic factors are regulated by repetitive exposure to suberythemal doses of different types of UV (UVA, UVB or SSR). Six volunteers with skin type II-III were irradiated with SSR, UVA or UVB radiation for 2 weeks (5 times per week, 10 times total) after preliminary determination of their MEDs. Biopsies were taken 3 days after the last irradiation.

ORGANISM(S): Homo sapiens

SUBMITTER: Vincent Hearing

PROVIDER: E-GEOD-21429 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

Regulation of human skin pigmentation in situ by repetitive UV exposure: molecular characterization of responses to UVA and/or UVB.

Choi Wonseon W Miyamura Yoshinori Y Wolber Rainer R Smuda Christoph C Reinhold William W Liu Hongfang H Kolbe Ludger L Hearing Vincent J VJ

The Journal of investigative dermatology 20100211 6

UV radiation is a major environmental factor that affects pigmentation in human skin and can eventually result in various types of UV-induced skin cancers. The effects of various wavelengths of UV on melanocytes and other types of skin cells in culture have been studied, but little is known about gene expression patterns in situ following in situ exposure of human skin to different types of UV (UVA and/or UVB). Paracrine factors expressed by keratinocytes and/or fibroblasts that affect skin pigm ...[more]

PMID: 20147966

Similar Datasets

Project description:Ultraviolet (UV) wavebands in sunlight are immunomodulatory. About half the amount of UVA within a minimum erythemal dose of sunlight is systemically immunosuppressive, while higher doses protect from UVB immunosuppression in mice. We have previously shown that these responses to UVA are genetically restricted as they occur in C57BL/6 but not Balb/c mice. We used gene set enrichment analysis of microarray data and real-time RT-PCR confirmation to determine the molecular mechanisms associated with UVA immunomodulation. We found up-regulation of mRNA for the alternative complement pathway. The core-enriched genes complement component 3, properdin and complement factor B were all activated by the immunosuppressive dose of UVA only in UVA-responsive C57BL/6 but not unresponsive BALB/c mice. This therefore matched the genetic restriction and dose responsiveness of UVA immunosuppression. The immune-protective higher UVA dose prevented UVB from down regulating chemokine receptor 7 and IL-12B, and decreased IL-10, supporting previous identification of IL-12 and IL-10 in high dose UVA protection from UVB immunosuppression. Our study has identified activation of the alternative complement pathway as a trigger of UVA-induced systemic immunosuppression and suggests that this pathway is likely to be an important sensor of UVA-induced damage to the skin. 24 hours after UVA, UVB and ssUV irradiation, a 1 cm2 uniform section of skin was excised from the dorsal surface of irradiated and control mice. Total RNA was then extracted from the whole skin using TRIzol reagent (Gibco Invitrogen Life Technologies, Carlsbad, CA, USA) according to the manufacturerâ??s instructions, purified, DNase treated and reverse transcribed into cDNA. For the microarray study a direct incorporation of Cyanine 3-dCTP and Cyanine 5-dCTP fluorescent dyes (Perkin Elmer Life Sciences, Inc. Boston, MA, USA) was used for cDNA synthesis. For each UV dose, a reference design was used to compare an unirradiated control against an irradiated sample. Microarray experiments used compugen 22k mouse oligonucleotide microarray slides (The Clive and Vera Ramaciotti Centre for Gene Function Analysis, Sydney Australia (http://www.ramaciotti.unsw.edu.au). Lower and higher UVA doses were used. C57BL/6 mice were irradiated with lower UVA, higher UVA, UVB, or ssUV; Balb/C mice were irradiated with lower or higher UVA. Experiments were replicated 6 times for each UV dose. A fluorescent dye swap was done for each alternate hybridisation to reduce systematic dye bias of incorporated fluorescent dyes.

Project description:UVA1 makes up ~75% terrestrial ultraviolet radiation (UVR) is increasingly being used for the treatment for inflammatory skin disorders. It is also the major UVR spectral source in tanning lamps, however we lack human data to understand its effects on gene expression and further consequences. Using erythemally equivalent doses of UVA1 (50J/cm2) and UVB (30mJ/cm2) ~1MED (minimal erythema dose), this study examines time dependent whole genome expression, mRNA and protein changes in 12 skin types I/II individuals. The top upregulated pathway at 6h is inflammation through IL17 signaling for UVA1 (p=1.16e-6) and UVB (p=2.1e-4). At 24h the top upregulated pathway is extracellular matrix remodeling for UVA1 (p=5.5e-7) and UVB (p=2.9e-22). We show key spectral differences with matrix metalloproteinases (MMP): UVB upregulates MMP1 mRNA (p=0.0062), MMP3 mRNA (p=0.0016), MMP10 mRNA (p=0.028) at 24h compared to UVA1, MMP12 mRNA is upregulated by UVA1 at 6h and not by UVB (p=0.02). In a further 3 skin type I/II we show that MMP12 protein is formed by UVA1 (p=0.04) at 24h and that DQM-bM-^DM-" collagen type IV(likely MMP12 activity) hydrolysis occurs by UVA1 (p=0.027) at 10h. DQM-bM-^DM-" collagen type I hydrolysis occurs predominantly by UVB at 24h (p=0.031). Both UVA1 and UVB upregulate MMP1 at 10h and 24h. There is more MMP1 and MMP12 protein and activity in the epidermis than in dermis in all volunteers. We conclude that the biological processes that occur after 24h in human skin in vivo in response to erythemally equivalent doses of UVA1 and UVB are similar however there are key spectral differences: UVB plays a larger role in upregulating key MMPs in the epidermis. MMP12 is a UVA1 specific biomarker found predominantly in the epidermis and maybe useful as a marker of UVA1 exposure. We hypothesise that its formation by UVA1 could be related to the ability of UVA1 to produce significantly more oxidatively generated DNA than UVB (8oxodG). 47 samples were processed. The RNA was isolated from human skin samples of individual donors pre- or post irradiation with UVA or UVB. Skin biopsies were taken either before, 6h post, or 24h post exposure. Different doses of UVA were applied. Each condition was available from five or nine individuals, as indicated in the samples description below.

Dataset Information

Regulation of human skin pigmentation in situ by repetitive UV exposure - Molecular characterization of responses to UVA, UVB and SSR

Publications

Regulation of human skin pigmentation in situ by repetitive UV exposure: molecular characterization of responses to UVA and/or UVB.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets