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8‐Methoxypsoralen and Ultraviolet A Radiation Activate the Human Elastin Promoter in Transgenic Mice: In vivo and in vitro Evidence for Gene Induction
Author(s) -
Bernstein Eric F.,
Gasparro Francis P.,
Brown Douglas B.,
Takeuchi Tsunemichi,
Kong Sung K.,
Uitto Jouni
Publication year - 1996
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1996.tb02473.x
Subject(s) - elastin , photoaging , human skin , in vivo , in vitro , transgene , chloramphenicol acetyltransferase , elastic fiber , genetically modified mouse , dermis , chemistry , premature aging , microbiology and biotechnology , cancer research , biology , promoter , gene , gene expression , biochemistry , genetics , anatomy
Treatment of skin diseases with the combination of 8‐methoxypsoralen and ultraviolet A radiation (PUVA) results in clinical alterations in treated skin that resemble those observed in chronically photodamaged skin. The PUVA‐treated patients develop nonmelanoma skin cancers, pigmentary alterations and wrinkling characteristic of sun‐induced changes. The major alteration in the dermis of sun‐damaged skin is the deposition of abnormal elastic fibers, termed solar elastosis. Up‐regulation of elastin promoter activity in dermal fibroblasts explains the excess elastic tissue but not the reason for the aberrant morphology of the elastotic material. In order to study photoaging in an experimental system, we utilized a transgenic mouse line that expresses the human elastin promoter/chloramphenicol acetyltransferase construct in a tissue‐specific and developmentally regulated manner. Although UVB radiation has been demonstrated to increase promoter activity in vitro , UVA fails to demonstrate a similar effect at the doses utilized. In this study, we demonstrate the ability of PUVA treatment to up‐re‐gulate elastin promoter activity both in vitro and in vivo. These data help to explain the development of photoaging in sun‐protected PUVA‐treated skin. We attribute the up‐regulation of elastin promoter activity in response to PUVA to the formation of DNA photoadducts, which do not occur in response to UVA radiation alone.