ABSTRACT
BACKGROUND: Excessive skin exposure to solar radiation damages proteins and DNA, ultimately leading to skin ageing and cancers. OBJECTIVES: To identify new ultraviolet B (UVB) target genes to understand the mechanisms behind the detrimental effects of UVB. METHODS: Organotypic, stratified cultures of rat keratinocytes were exposed to UVB and analysed using a genome-wide expression array, quantitative real-time polymerase chain reaction and histology. The most downregulated gene, rClca2, was further characterized in rat keratinocytes and mouse skin models. RESULTS: A single, 30 mJ cm(-2) dose of broadband UVB proved effective in the organotypic epidermal culture. The expression of 627 genes was changed 24 h postirradiation. In silico analysis of the data indicated activation of DNA repair, metabolism, cell cycle control and amino acid metabolism, but only limited inflammation under these conditions. We selected for further investigation the most downregulated gene, rClca2, previously suggested to regulate keratinocyte differentiation and adhesion, and found that UVB caused a long-lasting downregulation in its expression. Both the rClca2 full-length isoform (expressed in the differentiating cells) and the truncated isoform (expressed in the basal layers) were reduced by UVB. Immunohistochemistry of mouse skin samples with isoform-specific antibodies showed a similar, epidermal differentiation-related pattern. In mouse specimens exposed to chronic ultraviolet radiation (UVR) the staining intensities were reduced and the differentiation-related isoform was disturbed in the hyperplastic and carcinomatous areas induced by UVR. CONCLUSIONS: The data show that rClca2 is a novel UVB target gene and suggest that it might play a role in epidermal differentiation and UV-dependent skin malignancies.
Subject(s)
Chloride Channels/radiation effects , Epidermis/radiation effects , Ultraviolet Rays , Animals , Cell Differentiation/radiation effects , Cells, Cultured , Chloride Channels/metabolism , Dose-Response Relationship, Radiation , Down-Regulation , Epidermal Cells , Epidermis/metabolism , Genome-Wide Association Study , Humans , Keratinocytes/radiation effects , Mice , RNA/metabolism , Rats , Transcription Factors/radiation effectsABSTRACT
Effects of 13 different yellow, orange and red (Schott) longpass filter glasses on the extrafoveal thresholds obtained by 3 normal subjects after dark-adaptation were measured using a Goldman-Weekers adaptometer. When filters GG400, GG420, GG435, GG455, GG475, GG495, OG515 and OG530 (cutting off radiation up to 527 nm) were used there was no significant change in the threshold value. However, significantly higher threshold values were obtained with the use of the filters OG550, OG570, OG590, RG610 and RG630.
