JLE

European Journal of Dermatology

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Molecular aspects of photoaging Volume 7, issue 3, April - May 1997

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Authors
Departments of Dermatology and Cutaneous Biology, and Biochemistry and Molecular Pharmacology, Jefferson Medical College, and the Jefferson Institute of Molecular Medicine, Thomas Jefferson University, 233 South 10th Street, Suite 450, Philadelphia, Pennsylvania, 19107, USA.

Evidence from several lines of investigation has indicated that extrinsic aging, when superimposed on the intrinsic aging processes, plays the major role in age-associated degenerative changes of the skin. The extrinsic aging is primarily due to ultraviolet irradiation (UV), and thus is known as photoaging. Histopathologic, immunohistochemical and ultrastructural observations have demonstrated that dermal accumulation of elastotic material is a characteristic feature of photoaging. Subsequent biochemical and molecular studies have revealed that activation of elastin gene expression, with enhancement of transcriptional activity of other extracellular matrix genes, is an early event in photoaging. Based on this premise, we have recently developed a line of transgenic mice, which expresses the human elastin promoter, linked to a chloramphenicol acetyltransferase reporter gene, in a tissue-specific and developmentally regulated manner. Exposure of the skin of these animals to UV, particularly UVB, resulted in enhancement of elastin promoter activation. Irradiation of fibroblast cultures established from the skin of these animals revealed a significant effect by UVB while UVA had no effect. However, exposure of the cultures to UVA together with 8-methoxypsoralen resulted in a marked enhancement of the activity. Collectively, our results confirm the role of UVB in the development of solar elastosis and further identify UVA as a contributing factor in vivo. The transgenic mouse model serves as a useful system to study mechanisms of cutaneous photoaging and provides a convenient model to test compounds that may protect the skin against photodamage.