TRANSFORMING GROWTH-FACTOR-BETA STIMULATES TROPHOBLAST ONCOFETAL FIBRONECTIN SYNTHESIS IN-VITRO - IMPLICATIONS FOR TROPHOBLAST IMPLANTATION IN-VIVO
TRANSFORMING GROWTH-FACTOR-BETA STIMULATES TROPHOBLAST ONCOFETAL FIBRONECTIN SYNTHESIS IN-VITRO - IMPLICATIONS FOR TROPHOBLAST IMPLANTATION IN-VIVO
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DOI：
10.1210/jc.78.5.1241
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发表时间：
1994-05-01
影响因子：
5.8
通讯作者：
WANG, CL
中科院分区：
文献类型：
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作者：
FEINBERG, RF;KLIMAN, HJ;WANG, CL
在妊娠组织中，癌胎儿纤维连接蛋白（onfFN）特异性定位于胎盘-子宫交界处和绒毛膜周围的细胞外基质（ECM）。当从妊娠早期或晚期胎盘中分离出来时，培养的人细胞滋养细胞在ECM中分泌并沉积onfFN。此外，onfFN的合成在血清刺激因子的作用下显著上调。本研究的目的是研究转化生长因子- β (TGF β)的作用，TGF β是子宫蜕膜中存在的一种细胞因子，作为滋养细胞onfFN产生的刺激物。我们最初对TGF β的意义的认识是由于偶然使用了一名患有严重同种免疫性血小板减少症的新生儿的脐带血。在含有该血清的培养基中培养的滋养细胞形态分化正常，但产生的onfFN明显减少。以类似的方式，用抗tgf β中和抗体在正常血清中培养的滋养细胞也显著减少onfFN的产生。在含有血小板减少血清的培养基中，外源性添加TGF β 1可使滋养细胞产生onfFN的能力恢复4- 5倍。在从人或牛血浆中提取的血小板缺乏血清中，TGF β 1也能诱导onfFN合成，这一结果在条件培养基和细胞相关ECM原纤维中onfFN的免疫细胞化学定位中得到验证。剂量-反应分析表明，onfFN刺激反应对TGF β敏感，ED（50）为0.1-0.2 ng/ml。以互惠的方式，TGF β抑制β hCG分泌3- 4倍。我们的研究结果表明，TGF β是滋养细胞onfFN产生的重要刺激物。此外，TGF β似乎通过上调锚定滋养细胞标记物（onfFN）的表达和下调绒毛合胞滋养细胞表型标记物（hCG β）来调节滋养细胞分化。我们推测，在植入环境中，滋养细胞对TGF β的反应性通过刺激滋养细胞衍生的植入部位纤维连接蛋白的产生，促进了滋养细胞的粘附。
In pregnancy tissues, oncofetal fibronectin (onfFN) has been localized specifically to the extracellular matrix (ECM) surrounding extravillous anchoring trophoblasts of the placental-uterine junction and chorion. When isolated from first or third trimester placentas, human cytotrophoblasts in culture secrete and deposit onfFN in the ECM. In addition, onfFN synthesis is significantly up-regulated in response to serum stimulatory factor(s). The goal of this study was to examine the role of transforming growth factor-beta (TGF beta), a cytokine present in uterine decidua, as a stimulator of trophoblast onfFN production. Our initial insight into the significance of TGF beta resulted from the serendipitous use of cord serum from a neonate with severe alloimmune thrombocytopenia. Trophoblasts cultured in medium containing this serum underwent normal morphological differentiation, but produced markedly less onfFN. In an analogous fashion, trophoblasts cultured in normal serum preincubated with anti-TGF beta neutralizing antibodies also produced significantly less onfFN. Exogenously added TGF beta 1 restored the ability of trophoblasts to produce onfFN by a factor of 4-to 5-fold in medium containing thrombocytopenic serum. In platelet poor serum derived from human or bovine plasma, TGF beta 1 also induced onfFN synthesis, as assayed both in the conditioned medium and by immunocytochemical localization of onfFN in cell-associated ECM fibrils. Dose-response analysis demonstrated that the onfFN stimulatory response is sensitive to TGF beta, with an ED(50) of 0.1-0.2 ng/ml. In a reciprocal fashion, TGF beta inhibited beta hCG secretion 3- to 4-fold. Our results demonstrate that TGF beta is a significant stimulator of trophoblast onfFN production. Furthermore, TGF beta appears to modulate trophoblast differentiation by up-regulating the expression of an anchoring trophoblast marker (onfFN) and down-regulating a phenotypic marker of villous syncytiotrophoblast (hCG beta). We speculate that trophoblast responsiveness to TGF beta in the implantation milieu contributes to trophoblast adhesion by stimulating the production of a trophoblast-derived implantation site fibronectin.