滋养细胞侵袭能力降低是子痫前期(PE)的发病基础。ACTN4作为骨架蛋白参与了网格蛋白(Clathrin)介导的内吞作用(CME)，进而通过PI3K/Akt通路调控绒毛外滋养细胞(EVT)的侵袭。课题组前期在PE胎盘组织中证实ACTN4、Clathrin表达降低，PI3K/Akt通路活性明显下降，表明ACTN4降低可能是导致EVT侵袭力减弱并最终导致PE发生的原因之一。由此提出科学假设：“EVT中ACTN4表达下调，导致CME异常，Clathrin表达减少，PI3K活性下降，进而引起PI3K/Akt通路活化受损，造成EVT侵袭能力降低，导致PE”。项目拟以PE滋养细胞为研究对象，以细胞骨架异常为切入点，在组织、细胞及小鼠模型水平上应用分子生物学及基因工程等方法，从“胎盘组织-细胞-整体”全面验证该假说，将为深入研究PE的发病机制提供新思路。

The morbidity foundation of of pre-eclampsia (PE) is decreased invasive power in the trophoblast. As one of skeleton protein, ACTN4 involved in Clathrin mediated endocytosis (CME) modulates invasion of extravillous trophoblast (EVT) via PI3K/Akt pathway. Our earlier study identified that the expression of ACTN4 and Clathrin were down-regulated and the activity of PI3K/Akt signaling was reduced in the placenta tissue of PE patients, indicating the loss of ACTN4 may result in lower invasive power in the EVT and further cause PE occurrence. Based on those above, we hypothesize that decreased expression of ACTN4 leads to an aberrant CME course with Clathrin loss and a failure of PI3K/Akt signaling pathway by interfering PI3K activation to reduce invasion of EVT, thus inducing PE events. The project’s plan is that regarding the trophoblast cells from PE as the research object and the cytoskeletal abnormalities as the starting point, we will fully validate the hypothesis from part to whole by the application of molecular biology and genetic engineering methods in tissue, cell and mouse model level.