Ultraviolet radiation activates the human elastin promoter in transgenic mice: a novel in vivo and in vitro model of cutaneous photoaging.
The major alteration in photoaged skin is the deposition of massive amounts of abnormal elastic material, termed solar elastosis. In previous work, it has been shown that solar elastosis is accompanied by increased abundance of elastin and fibrillin mRNAs and upregulation of elastin promoter activity. Using a transgenic mouse line, which expresses the human elastin promoter, linked to a chloramphenicol acetyltransferase reporter gene, in a tissue-specific and developmentally regulated manner, we investigated the effects of ultraviolet A radiation and ultraviolet B radiation on human elastin promoter activity in vivo and in vitro. Irradiation of mice with a single dose of ultraviolet B radiation (491.4 mJ/cm2) resulted in an increase up to 8.5-fold in promoter activity, whereas a more modest increase of 1.8-fold was measured with ultraviolet A radiation (38.2 J/cm2). In addition, in vitro studies revealed over a thirtyfold increase in elastin promoter activity in response to ultraviolet B radiation (5.5 mJ/cm2), whereas no change was measured in response to ultraviolet A radiation (2.2 J/cm2). These results confirm the role of ultraviolet B radiation in elastin promoter activation in photoaging, and identify ultraviolet A radiation as a contributing factor. This system should serve as a useful in vivo and in vitro model to study cutaneous photoaging, and for testing compounds that may protect against cutaneous photodamage.
Bernstein
E F
EF
Department of Dermatology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Brown
D B
DB
Urbach
F
F
Forbes
D
D
Del Monaco
M
M
Wu
M
M
Katchman
S D
SD
Uitto
J
J
D000818:Animals; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D004548:Elasticity / Q000528:radiation effects*; D004549:Elastin / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D012867:Skin / Q000528:radiation effects*; D013997:Time Factors; D014466:Ultraviolet Rays
D004549:Elastin; D015500:Chloramphenicol O-Acetyltransferase