All-trans-retinoic acid down-regulates elastin promoter activity elevated by ultraviolet B irradiation in cultured skin fibroblasts.
Topical tretinoin therapy produces clinical improvements in the fine wrinkling of photodamaged skin, possibly by enhancement of collagen synthesis. A major biochemically and histologically detectable change in photodamaged skin is the accumulation of abnormal elastic fibers (elastotic material). However, little is known about the effects of retinoic acid and ultraviolet B (UVB) on elastin gene expression. Consequently, we examined the effects of all-trans-retinoic acid (t-RA) and UVB on elastin gene expression in cultured human skin fibroblasts in vitro. Elastin mRNA gene expression was up-regulated in response to UVB by approximately equal to 3-fold, in a dose dependent manner, between 3 and 10 mJ/cm2 doses. Similar results were obtained by chloramphenicol acetyltransferase assay, in which a maximal promoter activation more than 5.4-fold that in nonirradiated controls occurred after a single dose of 20 mJ/cm2. Also t-RA inhibited the increase in elastin mRNA level following a single exposure to UVB by approximately 16%, and the increase in promotor activity by about 65%. The inhibitory effect of t-RA on elastin induced by UVB was also demonstrated by indirect immunofluorescence studies. Taken together, t-RA down-regulated human elastin gene expression elevated by a single exposure to UVB at transcriptional and possibly protein levels. These results suggest that the anti-photoaging effect of t-RA may be related, at least in part, to down-regulation of elastin gene expression elevated by UVB.
Lee
K S
KS
Department of Dermatology, Keimyung University School of Medicine, Taegu, South Korea.
Kim
S J
SJ
Ryoo
Y W
YW
Kim
B C
BC
D000328:Adult; D015152:Blotting, Northern; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D015536:Down-Regulation / Q000187:drug effects; D004549:Elastin / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D014212:Tretinoin / Q000494:pharmacology*; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000528:radiation effects
D012333:RNA, Messenger; D014212:Tretinoin; D004549:Elastin; D015500:Chloramphenicol O-Acetyltransferase