Guller S, Kong L, Wozniak R, Lockwood C J
Department of Obstetrics/Gynecology, Mount Sinai Medical Center, New York, New York 10029, USA.
J Clin Endocrinol Metab. 1995 Jul;80(7):2244-50. doi: 10.1210/jcem.80.7.7608287.
Low levels of expression of extracellular matrix (ECM) proteins in chorioamniotic membranes is a characteristic of prematurely ruptured membranes, a condition associated with 40% of preterm deliveries. In light of the rise in levels of glucocorticoids (GC) in amniotic fluid associated with preterm labor, in the present study we examined the effects of GC on the expression of major ECM proteins in cultures of amnion epithelial cells recovered after digestion of human term amnions. Amnion cells were maintained with and without 10(-7) mol/L dexamethasone (DEX), and levels of the ECM protein fibronectin (FN) were determined by enzyme-linked immunosorbent assay. DEX treatment reduced FN expression in amnion epithelial cells to 15-30% of control levels and reduced FN expression in placental cells to 30-50% of control levels. Conversely, DEX treatment weakly stimulated FN expression in chorion cell cultures. DEX treatment did not affect the total level of amnion cell protein, indicating that the effects of DEX in amnion cells did not result from a general reduction in protein synthesis. Cortisol and DEX reduced FN expression in amnion cells, with half-maximal effective concentrations of approximately 60 and 8 nmol/L, respectively. In immunoprecipitation studies, DEX treatment reduced FN and collagen III synthesis to 20% of control levels, suggesting that GC may coordinately reduce the synthesis of major ECM proteins in amnion cells. Similarly, DEX treatment reduced the levels of FN messenger ribonucleic acids in amnion cells to approximately 15% of control levels. DEX treatment also promoted a marked reduction in FN expression in amnion cells cultured in serum-free medium to 10-50% of control levels. Our results indicate that GC negatively regulate ECM protein expression in amnion epithelial cells, suggesting a potential role in the genesis of altered fetal membrane ECM protein expression associated with prematurely ruptured membranes.
绒毛羊膜中细胞外基质（ECM）蛋白低水平表达是胎膜早破的一个特征，该病症与40%的早产相关。鉴于早产时羊水中糖皮质激素（GC）水平升高，在本研究中，我们检测了GC对人足月羊膜消化后获得的羊膜上皮细胞培养物中主要ECM蛋白表达的影响。羊膜细胞在有和没有10(-7) mol/L地塞米松（DEX）的情况下进行培养，通过酶联免疫吸附测定法测定ECM蛋白纤连蛋白（FN）的水平。DEX处理使羊膜上皮细胞中FN表达降至对照水平的15 - 30%，使胎盘细胞中FN表达降至对照水平的30 - 50%。相反，DEX处理对绒毛膜细胞培养物中FN表达有微弱刺激作用。DEX处理不影响羊膜细胞蛋白的总量，表明DEX对羊膜细胞的作用并非源于蛋白质合成的普遍减少。皮质醇和DEX降低羊膜细胞中FN表达，半数最大效应浓度分别约为60和8 nmol/L。在免疫沉淀研究中，DEX处理使FN和胶原蛋白III合成降至对照水平的20%，表明GC可能协同降低羊膜细胞中主要ECM蛋白的合成。同样，DEX处理使羊膜细胞中FN信使核糖核酸水平降至对照水平的约15%。DEX处理还促使无血清培养基中培养的羊膜细胞中FN表达显著降低至对照水平的10 - 50%。我们的结果表明，GC对羊膜上皮细胞中ECM蛋白表达起负调节作用，提示其在与胎膜早破相关的胎儿膜ECM蛋白表达改变的发生过程中可能发挥潜在作用。
