ENHANCED ELASTIN AND FIBRILLIN GENE-EXPRESSION IN CHRONICALLY PHOTODAMAGED SKIN

Cutaneous aging consists of chronologic aging as well as actinic damag e, referred to as photoaging. Most of the morphologic changes associat ed with an aged appearance result hom actinic damage to the skin. The morphologic changes in sun-damaged skin are associated with accumulati on of material having the staining characteristics of elastin, known a s solar elastosis, in the superficial dermis. Previous studies have de monstrated the presence of elastin within areas of solar elastosis; ho wever, little is known about the mechanisms leading to elastin accumul ation in photoaged skin. In addition, fibrillin, the fibrillar compone nt of elastic fibers, has been found in small amounts in solar elastos is. In this study we demonstrate increased elastin mRNA levels in phot oaged skin, as well as increased elastin and fibrillin mRNAs in skin e xplant-derived fibroblasts using Northern hybridizations, compared wit h controls from sun-protected sites of the same individual. Increased elastin mRNA levels result from transcriptional upregulation of the ge ne, as demonstrated by transient transfections with a human elastin pr omoter/chloramphenicol acetyltransferase construct. Elevated mRNA leve ls were also correlated with increased elastin and fibrillin depositio n in paired biopsy specimens from photodamaged and non-sun-exposed ski n, as demonstrated by immunohistochemical staining. Thus, approaches t o counteract transcriptional activation of elastin gene expression may be useful in preventing the changes associated with cutaneous photoag ing.