Supplemental.Up-regulation of CD81 inhibits cytotrophoblast invasion and mediates maternal endothelial cell dysfunction in preeclampsia
Supplemental.Up-regulation of CD81 inhibits cytotrophoblast invasion and mediates maternal endothelial cell dysfunction in preeclampsia
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CD81 的上调可抑制细胞滋养层侵袭并介导先兆子痫中的母体内皮细胞功能障碍。
DOI：
10.1073/pnas.1617601114
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发表时间：
2017-02-21
影响因子：
11.1
通讯作者：
Hu, Yali
中科院分区：
文献类型：
--
作者：
Shen, Li;Diao, Zhenyu;Hu, Yali
先兆子痫 (PE) 是由妊娠早期胎盘异常引起的，随后在妊娠中期或晚期 (TM) 母体小动脉内皮细胞的系统性激活。在正常妊娠期间，胎盘细胞滋养层（CTB）侵入母体子宫壁和螺旋动脉，而在PE中这一过程被中断。然而，目前尚不清楚畸形胎盘如何引发母体内皮危机及相关表现。在这里，我们重点关注 CD81 与 PE 的关联。 CD81 是四跨膜蛋白超家族的成员，在细胞生长、粘附和运动中发挥重要作用。 CD81 在人类胎盘形成中的功能及其与妊娠并发症的关系目前尚不清楚。在本研究中，我们证明 CD81 优先在正常第一 TM 胎盘中表达，并随着妊娠提前逐渐下调。在早发性严重 PE (sPE) 患者中，合体滋养层 (STB)、CTB 和绒毛核心细胞中 CD81 的表达显着上调。此外，在 sPE 患者的母体血清中观察到高水平的 CD81。 CTB 中过表达 CD81 显着降低了 CTB 侵袭，在高剂量外源 CD81 存在下培养原代人脐静脉内皮细胞 (HUVEC) 会导致体外血管生成和内皮细胞活化中断。重要的是，CD81 诱导的大鼠模型模仿了人类 PE 的表型。
Preeclampsia (PE) is initiated by abnormal placentation in the early stages of pregnancy, followed by systemic activation of endothelial cells of the maternal small arterioles in the late second or third trimester (TM) of pregnancy. During normal pregnancy, placental cytotrophoblasts (CTBs) invade the maternal uterine wall and spiral arteries, whereas this process is interrupted in PE. However, it is not known how the malformed placenta triggers maternal endothelial crisis and the associated manifestations. Here, we have focused on the association of CD81 with PE. CD81, a member of the tetraspanin superfamily, plays significant roles in cell growth, adhesion, and motility. The function of CD81 in human placentation and its association with pregnancy complications are currently unknown. In the present study, we have demonstrated that CD81 was preferentially expressed in normal first TM placentas and progressively down-regulated with gestation advance. In patients with early-onset severe PE (sPE), CD81 expression was significantly up-regulated in syncytiotrophoblasts (STBs), CTBs and the cells in the villous core. In addition, high levels of CD81 were observed in the maternal sera of patients with sPE. Overexpressing CD81 in CTBs significantly decreased CTB invasion, and culturing primary human umbilical vein endothelial cells (HUVECs) in the presence of a high dose of exogenous CD81 resulted in interrupted angiogenesis and endothelial cell activation in vitro. Importantly, the phenotype of human PE was mimicked in the CD81-induced rat model.