Guller S, Wozniak R, Kong L, Lockwood C J
Department of Obstetrics/Gynecology and Reproductive Science, Mount Sinai Medical Center, New York, New York 10029, USA.
J Clin Endocrinol Metab. 1995 Nov;80(11):3273-8. doi: 10.1210/jcem.80.11.7593437.
Alterations in the expression of extracellular matrix (ECM) proteins in the placenta and fetal membranes have been linked to parturition whether occurring before or at term. In the present study, we examined the individual and combined effects of transforming growth factor (TGF)-beta and dexamethasone (DEX) on the expression of oncofetal fibronectin (onfFN), i.e. a major ECM protein synthesized by placenta, in cytotrophoblasts isolated from human term placentas to establish a model system from which to evaluate the actions of positive and negative regulators of ECM protein expression in the human placenta. Cytotrophoblasts were maintained for 21=62 h in medium supplemented with 4% charcoal-stripped calf serum in the presence or absence of TGF-beta (2 ng/mL) and DEX (10(-7) mol/L). Levels of onfFN in culture media were determined by immunoassay. TGF-beta treatment alone induced approximately a 150% increase in media levels of onfFN after 21 and 45 h of culture when compared with control, whereas DEX treatment alone reduced levels of onfFN to 15% of control levels. Media levels of onfFN in cells treated with both TGF-beta and DEX were 40-90% of control levels. Similarly, treatment of cells with TGF-beta alone promoted a 100-250% increase in rates of FN synthesis and levels of FN messenger ribonucleic acid, whereas DEX treatment alone reduced these indices of FN expression to approximately 10% of control levels. In cells treated with TGF-beta and DEX, levels of ECM protein synthesis and FN messenger ribonucleic acid were between 30 and 100% of control values. Similar patterns of regulation of FN expression by TGF-beta and DEX were observed when experiments were carried out in serum-free medium. Our results suggest that during pregnancy, TGF-beta and glucocorticoids may be important opposing physiological regulators of placental ECM protein expression.
胎盘和胎膜中细胞外基质（ECM）蛋白表达的改变与分娩有关，无论分娩发生在足月前还是足月时。在本研究中，我们检测了转化生长因子（TGF）-β和地塞米松（DEX）对癌胚纤连蛋白（onfFN）表达的单独及联合作用，onfFN是胎盘合成的一种主要ECM蛋白，我们从人足月胎盘中分离出细胞滋养层细胞，建立一个模型系统，用以评估人胎盘ECM蛋白表达的正性和负性调节因子的作用。细胞滋养层细胞在添加4%活性炭处理的小牛血清的培养基中培养21至62小时，培养基中存在或不存在TGF-β（2 ng/mL）和DEX（10⁻⁷ mol/L）。通过免疫测定法测定培养基中onfFN的水平。与对照组相比，单独用TGF-β处理在培养21小时和45小时后，培养基中onfFN水平增加了约150%，而单独用DEX处理则将onfFN水平降低至对照水平的15%。同时用TGF-β和DEX处理的细胞中，onfFN的培养基水平为对照水平的40%至90%。同样，单独用TGF-β处理细胞可使纤连蛋白（FN）合成速率和FN信使核糖核酸水平增加100%至250%，而单独用DEX处理则将这些FN表达指标降低至对照水平的约10%。在用TGF-β和DEX处理的细胞中，ECM蛋白合成水平和FN信使核糖核酸水平为对照值的30%至100%。在无血清培养基中进行实验时，观察到TGF-β和DEX对FN表达的调节模式相似。我们的结果表明，在怀孕期间，TGF-β和糖皮质激素可能是胎盘ECM蛋白表达的重要生理性拮抗调节因子。
