Pierce R A, Mariencheck W I, Sandefur S, Crouch E C, Parks W C
Department of Medicine, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri.
Am J Physiol. 1995 Mar;268(3 Pt 1):L491-500. doi: 10.1152/ajplung.1995.268.3.L491.
The production of elastin, an essential extracellular matrix protein of terminal airway interstitium, occurs mostly during early development. Because glucocorticoids influence airway maturation, we studied the effect of dexamethasone (Dex) on tropoelastin expression during fetal lung development. Timed-pregnant rats were treated with Dex (1 mg/kg daily), and fetal lungs were collected 3 days later at 17, 19, and 21 days of gestation. Dex treatment resulted in about a threefold increase in tropoelastin mRNA levels at 19 days concomitant with accelerated airway development. By in situ hybridization, Dex treatment increased the number of tropoelastin-expressing cells and the level of tropoelastin mRNA per cell. In organ culture, Dex increased lung tropoelastin expression and augmented cortisol stimulation of tropoelastin expression. In fetal pulmonary artery smooth muscle cells, 10(-8) M Dex upregulated tropoelastin mRNA expression and increased tropoelastin promoter-chloramphenicol acetyl transferase activity in transient transfections. These data indicate that pharmacologically administered glucocorticoids transcriptionally upregulate fetal lung tropoelastin expression and suggest that steroid hormones may be important regulators of elastin production in vivo.
弹性蛋白是终末气道间质中一种重要的细胞外基质蛋白，其生成主要发生在早期发育阶段。由于糖皮质激素会影响气道成熟，我们研究了地塞米松（Dex）对胎儿肺发育过程中前弹性蛋白表达的影响。对处于特定孕期的大鼠每日给予Dex（1毫克/千克），在妊娠第17、19和21天，于给药3天后收集胎儿肺组织。Dex治疗导致在妊娠19天时前弹性蛋白mRNA水平增加约三倍，同时气道发育加速。通过原位杂交发现，Dex治疗增加了表达前弹性蛋白的细胞数量以及每个细胞的前弹性蛋白mRNA水平。在器官培养中，Dex增加了肺前弹性蛋白的表达，并增强了皮质醇对前弹性蛋白表达的刺激作用。在胎儿肺动脉平滑肌细胞中，10^(-8) M的Dex上调了前弹性蛋白mRNA表达，并在瞬时转染中增加了前弹性蛋白启动子 - 氯霉素乙酰转移酶活性。这些数据表明，药理学剂量的糖皮质激素可转录上调胎儿肺前弹性蛋白的表达，并提示类固醇激素可能是体内弹性蛋白生成的重要调节因子。
