Abstract

Intrauterine adhesions (IUAs), the leading cause of uterine infertility, are characterized by endometrial fibrosis. The management of IUA is challenging because the pathogenesis of the disease largely unknown. In this study, we demonstrate that the mRNA and protein levels of high mobility group AT-hook 2 (HMGA2) were increased by nearly 3-fold (P < 0.0001) and 5-fold (P = 0.0095) in the endometrial epithelial cells (EECs) of IUA patients (n = 18) compared to controls. In vivo and in vitro models of endometrial fibrosis also confirmed the overexpression of HMGA2 in EECs. In vitro cell experiments indicated that overexpression of HMGA2 promoted the epithelial–mesenchymal transition (EMT) while knockdown of HMGA2 reversed transforming growth factor-β-induced EMT. A dual luciferase assay confirmed let-7d microRNA downregulated HMGA2 and repressed the pro-EMT effect of HMGA2 in vitro and in vivo. Therefore, our data reveal that HMGA2 promotes IUA formation and suggest that let-7d can depress HMGA2 and may be a clinical targeting strategy in IUA.

中文翻译：

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HMGA2诱导的上皮-间质转化在宫腔粘连中被let-7d逆转

 抽象的

子宫内膜粘连（IUAs）是子宫不孕的主要原因，其特征是子宫内膜纤维化。 IUA 的治疗具有挑战性，因为该疾病的发病机制很大程度上未知。在本研究中，我们证明子宫内膜上皮细胞中高迁移率基团 AT-hook 2 (HMGA2) 的 mRNA 和蛋白水平增加了近 3 倍（ P < 0.0001）和 5 倍（ P = 0.0095）。 IUA 患者 (n = 18) 与对照组相比的 EEC）。子宫内膜纤维化的体内和体外模型也证实了 HMGA2 在 EEC 中的过度表达。体外细胞实验表明，HMGA2 的过表达促进了上皮-间质转化 (EMT)，而 HMGA2 的敲低则逆转了转化生长因子-β 诱导的 EMT。双荧光素酶测定证实，let-7d microRNA 下调 HMGA2，并在体外和体内抑制 HMGA2 的促 EMT 作用。因此，我们的数据表明，HMGA2 促进 IUA 形成，并表明 let-7d 可以抑制 HMGA2，可能是 IUA 的临床靶向策略。