The Role of Epithelial to Mesenchymal Transition in Human Amniotic Membrane Rupture.
The Role of Epithelial to Mesenchymal Transition in Human Amniotic Membrane Rupture.
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DOI：
10.1210/jc.2016-3150
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发表时间：
2017-04-01
期刊：
影响因子：
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通讯作者：
Chaudhuri G
中科院分区：
文献类型：
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作者：
Janzen C;Sen S;Lei MY;Gagliardi de Assumpcao M;Challis J;Chaudhuri G
羊膜的生化弱化是胎膜早破（PPROM）之前的一个主要因素，会导致早产。已知基质金属蛋白酶（MMPs）的激活在羊膜的胶原蛋白降解中起关键作用；然而，由MMP激活所诱导的上皮 - 间质转化（EMT）作为羊膜弱化的一种机制尚未得到研究。
测量与阴道分娩（VD）相关的羊膜上皮 - 间质转化，并与未临产剖宫产（CS）进行比较，以及评估使用上皮 - 间质转化的药理抑制剂和诱导剂时羊膜机械强度的变化，从而验证上皮 - 间质转化是促进羊膜破裂的关键生化事件这一假设。
（1）通过荧光激活细胞分选分析，与未临产剖宫产相比，从阴道分娩获取的羊膜中间质细胞相对于上皮细胞的数量显著增加（60%对10%）；（2）肿瘤坏死因子（TNF）-α刺激羊膜上皮细胞2天后，间质标志物波形蛋白的表达增加；（3）上皮 - 间质转化抑制剂依托度酸显著增加了羊膜破裂所需的时间和机械压力；（4）TNF -α和另一种药理上皮 - 间质转化诱导剂依沙吖啶减少了羊膜破裂所需的时间和机械压力，进一步证实间质表型显著弱化了羊膜。
这项工作表明羊膜细胞的上皮 - 间质转化与分娩有关，且上皮 - 间质转化降低了羊膜的抗张强度。这些发现提示上皮 - 间质转化在胎膜早破的病理生理学中起作用，并可能为开发预防早产的疗法提供依据。
我们评估了人羊膜中的上皮 - 间质转化，发现与未临产剖宫产相比，分娩和胎膜早破与羊膜上皮 - 间质转化增加有关。
Biochemical weakening of the amnion is a major factor preceding preterm premature rupture of membranes (PPROMs), leading to preterm birth. Activation of matrix metalloproteinases (MMPs) is known to play a key role in collagen degradation of the amnion; however, epithelial to mesenchymal transition (EMT) that is also induced by MMP activation has not been investigated as a mechanism for amnion weakening. To measure amniotic EMT associated with vaginal delivery (VD) compared with unlabored cesarean sections (CSs), and to assess changes in amniotic mechanical strength with pharmacologic inhibitors and inducers of EMT, thus testing the hypothesis that EMT is a key biochemical event that promotes amniotic rupture. (1) Amnions taken from VD contained a significantly increased number of mesenchymal cells relative to epithelial cells compared with unlabored CS by fluorescence-activated cell sorting analysis (60% vs 10%); (2) tumor necrosis factor (TNF)–α stimulation of amniotic epithelial cells increased expression of the mesenchymal marker vimentin after 2 days; (3) EMT inhibitor, etodolac, significantly increased the time and mechanical pressure required to rupture the amnion; and (4) TNF-α and another pharmacologic EMT inducer, ethacridine, decreased the time and mechanical pressure required for amnion rupture, further confirming that the mesenchymal phenotype significantly weakens the amnion. This work demonstrated amniotic cell EMT was associated with labor and EMT decreased the tensile strength of the amnion. These findings suggest a role for EMT in the pathophysiology of PPROM and may provide a basis for development of therapies to prevent preterm labor. We evaluated EMT in the human amnion and found that labor and PPROM are associated with increased amniotic EMT compared with unlabored cesarean delivery.