Enhanced elastin and fibrillin gene expression in chronically photodamaged skin.
Cutaneous aging consists of chronologic aging as well as actinic damage, referred to as photoaging. Most of the morphologic changes associated with an aged appearance result from actinic damage to the skin. The morphologic changes in sun-damaged skin are associated with accumulation of material having the staining characteristics of elastin, known as solar elastosis, in the superficial dermis. Previous studies have demonstrated the presence of elastin within areas of solar elastosis; however, little is known about the mechanisms leading to elastin accumulation in photoaged skin. In addition, fibrillin, the fibrillar component of elastic fibers, has been found in small amounts in solar elastosis. In this study we demonstrate increased elastin mRNA levels in photoaged skin, as well as increased elastin and fibrillin mRNAs in skin explant-derived fibroblasts using Northern hybridizations, compared with controls from sun-protected sites of the same individual. Increased elastin mRNA levels result from transcriptional upregulation of the gene, as demonstrated by transient transfections with a human elastin promoter/chloramphenicol acetyltransferase construct. Elevated mRNA levels were also correlated with increased elastin and fibrillin deposition in paired biopsy specimens from photodamaged and non-sun-exposed skin, as demonstrated by immunohistochemical staining. Thus, approaches to counteract transcriptional activation of elastin gene expression may be useful in preventing the changes associated with cutaneous photoaging.
Department of Dermatology, Jefferson Medical College, Philadelphia, PA 19107-5541.
E F
EF
Bernstein
Y Q
YQ
Chen
K
K
Tamai
K J
KJ
Shepley
K S
KS
Resnik
H
H
Zhang
R
R
Tuan
A
A
Mauviel
J
J
Uitto
D000368:Aged; D000375:Aging / Q000235:genetics / Q000502:physiology; D015152:Blotting, Northern; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D002908:Chronic Disease; D004549:Elastin / Q000235:genetics*; D000071837:Fibrillins; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D012867:Skin / Q000737:chemistry*; D013471:Sunburn / Q000235:genetics*; D014162:Transfection
D000071837:Fibrillins; D008840:Microfilament Proteins; D004549:Elastin; D015500:Chloramphenicol O-Acetyltransferase