子痫前期（PE）发病机制未明，滋养细胞侵袭不良可能是PE的主要原因之一。我们对PE患者胎盘组织进行甲基化芯片分析时，首次筛选到能抑制多种肿瘤细胞侵袭的甲基化水平差异基因FHIT，并已通过实验发现：1）PE患者胎盘和L-NAME诱导小鼠PE模型中FHIT表达水平均升高；2）FHIT能抑制滋养细胞侵袭；3）FHIT能抑制侵袭调控因子Slug。因此我们推测FHIT在胎盘中过表达可能与PE发病有关，提出“胎盘中FHIT过表达导致Slug信号通路受阻，引起滋养细胞侵袭不良，导致PE发病”的假设。本研究拟利用胎盘特异性基因敲除小鼠和人类临床资源，结合CHIP、免疫共沉淀手段，从细胞-在体-分子层面探索FHIT/Slug介导的滋养细胞功能变化在PE发生发展中的作用，及FHIT调控Slug的分子机理。以期证实FHIT升高是否调控PE发病，及揭示一个新的PE调控机制。

Preeclampsia (PE) is a life-threaten disease with uncovered the molecular mechanism. Impeded trophoblast invasion is involved in the pathogenesis of PE. We analyzed the DNA methylation profile in the PE placentae and the normal control, and found the hypomethylated FHIT in the human placentae with PE, which functions as an antioncogene and suppresses cancer cell invasion. Our preliminary studies further found that 1) the overexpression of FHIT protein levels were detected in the human placentae with PE and in the L-NAME induced PE mouse placentae; 2) the in vitro experiment demonstrated that FHIT impeded trophoblast invasion; 3) our pilot mechanistic study showed that FHIT repressed the expression of Slug, which was a key regulatory factor of cellular invasion. Therefore, we hypothesized that the overexpression of FHIT in placenta resulted in the hindered trophoblast invasion and PE by regulating Slug signaling pathway. We proposed to generate the placental specifically knock-out or over-expression mouse model, and the clinical primary cell line to investigate the role of FHIT/Slug in PE pathogenesis. We also proposed to perform the CHIP and pull-down assays to investigate the underlying mechanism. Our studies will reveal a novel mechanism in the pathogenesis of PE.