子痫前期（PE）是妊娠常见的严重并发症，母胎界面血管形成障碍被认为是其发病机制之一。已知间充质干细胞（MSC）具有调节血管形成功能，我们前期发现PE患者母胎界面MSC生长及功能异常与miR-16靶向CCNE1及VEGFA有关。我们还发现长链非编码RNA（LncRNA）MALAT1在PE患者蜕膜MSC中显著下调。LncRNA 可调控microRNA，生物信息学方法预测MALAT1能够结合miR-16。故推测：蜕膜MSC低表达MALAT1失去对miR-16的有效调控，从而抑制CCNE1及VEGFA表达，引起MSC生长受限和调节血管形成障碍而诱发PE。本项目将分析MALAT1对蜕膜MSC的影响；揭示MALAT1/miR-16调控蜕膜MSC影响血管形成的机制；体内评估MALAT1调控miR-16对子宫螺旋动脉重铸的作用。本项目的完成将为揭示PE的发病机制和寻求新的有效防治方法提供新思路和新技术。

Pre-eclampsia is a severe pregnancy-specific disorder. Defective angiopoiesis of maternal-fetal interface is one of the most favored pathogenesis. As is well known, mesenchymal stem cells (MSCs) have the function of regulating angiogenesis. In our previous studies, we found that MSCs from maternal-fetal interface of patients with PE presented slow growth and abnormal function which associated with miR-16 targeting CCNE1 and VEGFA expression. We also found that long non-coding RNA (LncRNA) MALAT1 was significantly deceresed in decidua derived MSCs from patients with PE. The functions of microRNA can be regulated by the LncRNA. We predicted that LncRNA MALAT1 can combine miR-16 using bioinformatics methods. We suppose that decreased MALAT1in decidua MSCs lost the effective regulation of miR-16, and then inhibit the expression of CCNE1 and VEGFA, which result in growth restriction and regulation of angiogenesis dysfunction of MSCs, and finally lead to the occurrence of PE. Our project is to investigate the effects of MALAT1 on MSCs’proliferation and function; to explore the mechanisms of MALAT1 in regulating decidua MSCs to affect angiogenesis via inhibiting miR-16; to assess the effects of MALAT1 on blood pressure, urine protein and other preeclampsia related indicators in miR-16 overexpressed pregnant rats. We will provide new insight and technology to understand pathogenesis of pre-eclampsia and find new effective method to prevent and cure this disease.