Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Mol Med Rep. 2019 Sep;20(3):2812-2822. doi: 10.3892/mmr.2019.10490. Epub 2019 Jul 12.
Zinc finger E‑box‑binding homeobox 1 (Zeb1) is a promoter of epithelial‑mesenchymal transformation, which may serve an important role in morbidly adherent placenta (MAP). In the present study, the protein expression levels of Zeb1 were examined in the placenta tissues of 60 patients, including 20 patients with placenta accreta (PA) and 20 patients with placenta previa without PA (UPA) and 20 patients in late pregnancy that delivered by cesarean section (normal). The expression levels of Zeb1, N‑cadherin, vascular endothelial growth factor (VEGF), Tumor necrosis factor‑related apoptosis‑inducing ligand‑receptor 2 (TRAIL‑R2), and tumor necrosis factor‑related apoptosis‑inducing ligand‑receptor 3 (TRAIL‑R3) were higher in PA tissues compared with in normal control tissues. The expression levels of E‑cadherin and TRAIL‑R2 were decreased in PA tissues compared with in normal control tissues. These findings indicated that Zeb1 may serve an important role in placental attachment, thus promoting the development of dangerous PA. Overexpression of Zeb1 may upregulate the expression levels of N‑cadherin, VEGF, TRAIL‑R3, cyclin D1 and Bcl‑2, and downregulate the expression levels of E‑cadherin and TRAIL‑R2. In addition, Zeb1 regulated the viability, apoptosis and migration of HTR‑8/SV neo cells and human umbilical vein endothelial cells by regulating the Akt pathway. In conclusion, these findings indicated that Zeb1 may promote placental implantation by activating the Akt signaling pathway, thus providing a theoretical basis for investigating the causes of MAP.
锌指 E-盒结合同源盒 1(Zeb1)是上皮-间充质转化的启动子,在病态粘连性胎盘(MAP)中可能发挥重要作用。本研究检测了 60 例胎盘组织中 Zeb1 的蛋白表达水平,包括 20 例胎盘植入(PA)患者、20 例无 PA 的前置胎盘(UPA)患者和 20 例剖宫产分娩的晚期妊娠患者(正常)。PA 组织中 Zeb1、N-钙黏蛋白、血管内皮生长因子(VEGF)、肿瘤坏死因子相关凋亡诱导配体受体 2(TRAIL-R2)和肿瘤坏死因子相关凋亡诱导配体受体 3(TRAIL-R3)的表达水平高于正常对照组。PA 组织中 E-钙黏蛋白和 TRAIL-R2 的表达水平低于正常对照组。这些结果表明,Zeb1 可能在胎盘附着中起重要作用,从而促进危险的 PA 的发展。Zeb1 的过表达可能上调 N-钙黏蛋白、VEGF、TRAIL-R3、细胞周期蛋白 D1 和 Bcl-2 的表达水平,下调 E-钙黏蛋白和 TRAIL-R2 的表达水平。此外,Zeb1 通过调节 Akt 通路调节 HTR-8/SV neo 细胞和人脐静脉内皮细胞的活力、凋亡和迁移。综上所述,这些结果表明,Zeb1 可能通过激活 Akt 信号通路促进胎盘植入,为研究 MAP 的病因提供了理论依据。