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E2‐mediated EMT by activation of β‐catenin/Snail signalling during the development of ovarian endometriosis

机译:在卵巢子宫内膜异位症发展过程中通过激活β-catenin/ Snail信号传导的E2介导的EMT

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摘要

Endometriosis is an oestrogen‐dependent disease, and epithelial‐mesenchymal transition (EMT) is involved in the process of endometriosis. Whether oestrogen could induce EMT in endometriosis remains largely unknown. Here, we reported that up‐regulated expression of EMT markers in ovarian chocolate cyst is accompanied by high expression 17β‐hydroxysteroid dehydrogenase 1 (17β‐HSD1), and exposure of primary human endometrial epithelial cells to oestradiol conditions could promote EMT occurrence and activate both β‐catenin and Snail signalling. Furthermore, we found nuclear β‐catenin and Snail expression was closely linked in ovarian endometriosis, and β‐catenin knockdown abrogated oestrogen‐induced Snail mediated EMT in vitro. This is due to that β‐catenin/ TCF‐3 could bind to Snail promoter and activate its transcription. These results suggested that β‐catenin signalling functions as the Snail activator and plays a critical role in oestradiol‐induced EMT in endometriosis.
机译:子宫内膜异位是一种依赖雌激素的疾病,子宫内膜异位的过程涉及上皮-间质转化(EMT)。雌激素是否可以在子宫内膜异位症中诱发EMT仍然未知。在这里,我们报道了卵巢巧克力囊肿中EMT标记的表达上调伴随着高表达的17β-羟基类固醇脱氢酶1(17β-HSD1),并且原代人子宫内膜上皮细胞暴露于雌二醇条件可以促进EMT的发生并激活两者β-catenin和Snail信号传导。此外,我们发现核内β-catenin和Snail的表达与卵巢子宫内膜异位症密切相关,而β-catenin的敲除在体外消除了雌激素诱导的Snail介导的EMT。这是因为β-catenin/ TCF-3可以与Snail启动子结合并激活其转录。这些结果表明,β-catenin信号传导起着Snail激活剂的作用,并且在雌二醇引起的子宫内膜异位症的EMT中起着关键作用。

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