Dehydroepiandrosterone에 의한 탄력소 유전자의 발현 조절

Abstract

Background : Dehydroepiandrosterone(DHEA) and its sulfate ester dehydro- epiandrosterone sulfate(DHEA-S) are the steroids secreted most abdundantly by the human adrenal gland, but the physiologic role remains uncertain . Elastin is one of the major extracellular matrix components of ant the dermis and plays an important role in providing elasticity and resilience of the skin. Expression of elastin gums at transcriptional level is regulated and modulated by cytokines, vitamin D3, insulin-like growth factor-1, and steroids But only little is known about the molecular and cellular mechanism underlying the effect of DHEA on the expression of elastin in cultured skin fibroblasts. Objective : The purpose of this study was to examine the effect of DHEA on elastin gene expression in cultured skin fibroblasts. Methods : In this study, the effects of DHEA were examined by Northern blot hybridization, chloramphenicol acetyltranferase assay (CAT). and laser scanning microscopy in cultured human fibroblasts. Results : In Northern blot hybridization, levels of elastin mRNA we, increased 1.5-fold at 1 nmol of DHEA, 4.2-fold at 0.1 μ㏖ and 6.5-fold at 10 μ㏖, compared to untreated control. DHEA caused a alteration in the elastin mRNA expression in a dose-related fashion. In CAT assay, the relative mRNA CAT activity was 0.9 at a concentration of 1 nmol 2.4 at 0.1 μmol, and 2.7 at a 10 μ㏖. DHEA caused a marked increase on elastin promotor activity. In confocal laser scanning microscopy. the immunosignal for elastin in DHEA-treated fibroblasts is more intense compared to the control. Conclusion : These results indicate that DHEA may be a powerful up-regulator of elastin production, suggesting transcriptional activation of gene expression in cultured skin fibroblasts.