Nur77 promotes embryo adhesion by transcriptionally regulating HOXA10 expression
Nur77 promotes embryo adhesion by transcriptionally regulating HOXA10 expression
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DOI：
10.1080/19396368.2019.1671536
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发表时间：
2020-01
影响因子：
2.4
通讯作者：
Jingtao Shen;Xudong Zhu;Mei Zhang;Yue Jiang;G. Yan;Zhilong Wang;Lihua Sun;Qun Zhang
中科院分区：
文献类型：
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作者：
Jingtao Shen;Xudong Zhu;Mei Zhang;Yue Jiang;G. Yan;Zhilong Wang;Lihua Sun;Qun Zhang
HOXA 10是胚胎粘附的重要调节因子。表达减少可能导致胚胎着床失败。Nur 77和HOXA 10的表达在复发性着床失败患者的子宫内膜中已显示出减少。在这项研究中，我们发现，Nur 77直接结合HOXA 10启动子，并促进HOXA 10蛋白的表达在石川细胞中以剂量依赖性的方式。当内源性HOXA 10表达被敲低时，Nur 77对石川细胞胚胎粘附的促进作用被显著阻断。此外，Nur 77激动剂6-MP也被证实促进胚胎粘附。这项研究首次表明Nur 77通过转录调节HOXA 10表达促进胚胎粘附。Nur 77和6-MP可能为开发一种新的治疗胚胎粘附功能障碍的方法提供依据。缩略语：HB-EGF：肝素结合表皮生长因子样生长因子; HOXA 10：同源框A10; NGFI-B：神经生长因子诱导基因B; RIF：复发性着床失败; RPL：复发性妊娠丢失; 6-MP：6-巯基嘌呤; IGFBP-1：胰岛素样生长因子结合蛋白-1; LIF：白血病抑制因子; IL-1β：白细胞介素-1 β; CRISPR/Cas9：规则间隔短回文重复序列; AF-1：激活功能-1域; HIF-1α：低氧诱导因子1α; CREB：cAMP反应元件结合
ABSTRACT HOXA10 is an important regulator of embryo adhesion. Reduced expression may contribute to embryo implantation failure. The expression of Nur77 and HOXA10 has been shown to be reduced in the endometrium of patients with recurrent implantation failure. In this study, we found that Nur77 was directly bound to the HOXA10 promoter and promoted HOXA10 protein expression in a dose-dependent manner in Ishikawa cells. Furthermore, the promoting effect of Nur77 on embryo adhesion was significantly blocked when endogenous HOXA10 expression was knocked down in Ishikawa cells. Moreover, the Nur77 agonist 6-MP was also confirmed to promote embryo adhesion. This study is the first to show that Nur77 promotes embryo adhesion by transcriptionally regulating HOXA10 expression. Nur77 and 6-MP may provide a basis to develop a new treatment for patients who suffer from embryo adhesion dysfunction. Abbreviations: HB-EGF: heparin-binding epidermal growth factor-like growth factor; HOXA10: homeobox A10; NGFI-B: nerve growth factor-induced gene B; RIF: recurrent implantation failure; RPL: recurrent pregnancy loss; 6-MP: 6-mercaptopurine; IGFBP-1: insulin-like growth factor binding protein-1; LIF: leukemia inhibitory factor; IL-1β: Interleukin - 1β; CRISPR/Cas9: Clustered Regularly Interspaced Short Palindromic Repeats; AF-1: activation function-1 domain; HIF-1α: hypoxia-inducible factor 1α; CREB: cAMP response element binding