Estrogen attenuates TGF-β1-induced EMT in intrauterine adhesion by activating Wnt/β-catenin signaling pathway
Estrogen attenuates TGF-β1-induced EMT in intrauterine adhesion by activating Wnt/β-catenin signaling pathway
复制标题
雌激素通过激活 Wnt/β-catenin 信号通路减弱 TGF-β1 诱导的宫腔粘连 EMT
DOI：
10.1590/1414-431x20209794
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发表时间：
2020-01-01
影响因子：
2.3
通讯作者：
Wei, Jun
中科院分区：
文献类型：
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作者：
Cao, Jia;Liu, Dan;Wei, Jun
尽管雌激素在子宫内膜生长中具有重要的功能，但其在宫内粘连（IUA）中的具体剂量和潜在的分子机制尚不清楚。在本研究中，我们旨在探讨雌激素对正常和纤维化子宫内膜上皮-间质转化（EMT）的影响，以及雌激素和Wnt/ β -catenin信号在子宫内膜纤维化形成中的作用。采用CCK-8和免疫荧光法观察不同浓度雌激素对正常人子宫内膜上皮细胞（hEECs）的增殖作用。采用qRT-PCR和western blot方法，探讨雌激素对正常和纤维化子宫内膜EMT的影响，以及体外Wnt/ β -catenin信号通路主要成分的影响。采用苏木精染色、伊红染色和马松染色观察雌激素对子宫内膜形态和纤维化的影响。我们的研究结果表明，30 nM浓度的雌激素抑制正常hEECs的增殖，并伴有间充质标记上调和上皮标记下调。有趣的是，在转化生长因子β 1 （tgf - β 1）诱导的子宫内膜纤维化模型中，相同浓度的雌激素抑制了EMT的过程，这可能部分是通过调节Wnt/ β -catenin通路介导的。此外，在IUA动物模型中，相对高剂量的雌激素有效地增加了子宫内膜腺的数量，减少了纤维化面积，这是通过减少EMT来确定的。综上所述，我们的研究结果表明，适当浓度的雌激素可能通过抑制tgf - β 1诱导的EMT和激活Wnt/ β -catenin通路来预防IUA的发生和发展。
Although estrogen has crucial functions for endometrium growth, the specific dose and underlying molecular mechanism in intrauterine adhesion (IUA) remain unclear. In this study, we aimed to investigate the effects of estrogen on epithelial-mesenchymal transition (EMT) in normal and fibrotic endometrium, and the role of estrogen and Wnt/beta-catenin signaling in the formation of endometrial fibrosis. CCK-8 and immunofluorescence assay were performed to access the proliferation of different concentrations of estrogen on normal human endometrial epithelial cells (hEECs). qRT-PCR and western blot assay were utilized to explore the effect of estrogen on EMT in normal and fibrotic endometrium, and main components of Wnt/beta-catenin signaling pathway in vitro. Hematoxylin and eosin and Masson staining were used to evaluate the effect of estrogen on endometrial morphology and fibrosis in vivo. Our results indicated that the proliferation of normal hEECs was inhibited by estrogen at a concentration of 30 nM accompanied by upregulation of mesenchymal markers and downregulation of epithelial markers. Interestingly, in the model of transforming growth factor beta 1 (TGF-beta 1)-induced endometrial fibrosis, the same concentration of estrogen inhibited the process of EMT, which might be partially mediated by regulation of the Wnt/beta-catenin pathway. In addition, relatively high doses of estrogen efficiently increased the number of endometrial glands and reduced the area of fibrosis as determined by the reduction of EMT in IUA animal models. Taken together, our results demonstrated that an appropriate concentration of estrogen may prevent the occurrence and development of IUA by inhibiting the TGF-beta 1-induced EMT and activating the Wnt/beta-catenin pathway.