Ultraviolet（ UV）-and UV-related cytokine-mediated transcriptional mechanisms of type VII collagen gene（ COL7A1） expression in the skin, with special reference to photoaged skin and anti-aging

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Chronic ultraviolet （UV） radiation results in photoaged skin characterized by deep wrinkle formation.Recent studies suggest that diminishment of anchoring fi brils（ AF）, stabilizing the association of the basement membraneto the underlying dermis, are involved in photoaged skin. Expression of COL7A1, encoding type VII collagen that is amajor component of AF, is also decreased in photoaged skin. In this study, we have investigated COL7A1 transcriptionby UV and UV-related cytokines involved in photoaged skin. Nuclear run-on assay, luciferase assay and gel shift assayrevealed that UV and UV-related cytokines（ TNF-α, IL-1β） tissue specifi cally downregulated COL7A1 transcription inepidermal keratinocytes, whereas COL7A1 transcription was upregulated by each modulator in dermal fi broblasts. Theresponsive element of each modulator was located between nucleotide -524 and -22 of COL7A1 promoter and AP-1 andNF-κB families band to this region. Taken together, these data strongly suggest that the downregulation of COL7A1transcription in epidermal keratinocytes, main cells expressing COL7A1 in the skin, and subsequent diminishment of AFare involved in photoaged skin. We also have discussed relation between these results and pathophysiology of wrinkleformation, characteristic feature of photoaged skin.
弘前大学の論文