Ledo I, Wu M, Katchman S, Brown D, Kennedy S, Hsu-Wong S, Uitto J
Department of Dermatology, Jefferson Medical College, Philadelphia, Pennsylvania 19107.
J Invest Dermatol. 1994 Nov;103(5):632-6. doi: 10.1111/1523-1747.ep12397669.
Recent characterization of the human elastin gene identified three putative glucocorticoid responsive elements (GRE) within the 5'-flanking DNA. To test the functionality of these cis-elements, transgenic mice that express a human elastin promoter-reporter gene (CAT) construct in a tissue-specific manner were injected with triamcinolone acetonide (TMC) or dexamethasone (DEX), two glucocorticosteroids in clinical use. Subcutaneous injection of these glucocorticoids resulted in a marked, up to 28-fold, enhancement of the CAT activity in the skin at the site of injection. Similarly, intraperitoneal injection of DEX resulted in significant increases in the elastin promoter activity in various internal organs. Furthermore, incubation of skin fibroblast and aortic smooth muscle cell cultures established from the transgenic animals with TMC (10 ng/ml) resulted in marked increases in the elastin promoter activity. These studies demonstrate that glucocorticosteroids act as powerful up-regulators of human elastin promoter activity in transgenic mice.
最近对人类弹性蛋白基因的特征分析在其5'侧翼DNA内鉴定出三个假定的糖皮质激素反应元件（GRE）。为了测试这些顺式元件的功能，将以组织特异性方式表达人类弹性蛋白启动子-报告基因（CAT）构建体的转基因小鼠注射曲安奈德（TMC）或地塞米松（DEX），这两种都是临床使用的糖皮质激素。皮下注射这些糖皮质激素导致注射部位皮肤中CAT活性显著增强，最高可达28倍。同样，腹腔注射DEX导致各种内部器官中弹性蛋白启动子活性显著增加。此外，用TMC（10 ng/ml）处理从转基因动物建立的皮肤成纤维细胞和主动脉平滑肌细胞培养物，导致弹性蛋白启动子活性显著增加。这些研究表明，糖皮质激素在转基因小鼠中是人类弹性蛋白启动子活性的强大上调因子。
