子痫前期（Preeclampsia，PE）是妊娠期特有的疾病，目前唯终止妊娠是最有效的治疗手段。研究其发病的分子机制，寻找新的分子标志物，对PE的早期预测和干预具有重要意义。申请人前期研究发现，组蛋白乙酰化酶CSRP2BP在PE患者胎盘组织中表达显著降低，且与PE患者的血压升高具有相关性。此外，在人滋养细胞HTR-8中沉默CSRP2BP能下调FOXA1表达，抑制细胞的增殖，迁移及侵袭。据此，申请人提出“CSRP2BP通过调控FOXA1表达，调节滋养细胞的功能，参与PE的发生发展”的假说。为证实该假说，本课题组拟建立沉默和过表达CSRP2BP的HTR-8细胞株和人诱导性多能干细胞株以及滋养细胞特异性敲除CSRP2BP的小鼠模型，在分子、细胞及个体水平，研究CSRP2BP对滋养细胞功能的调控作用及其在PE中的作用机制，并结合临床资料分析其与PE的相关性，有望为临床早期预测和治疗PE提供新靶标。

Preeclampsia (PE) is a gestation-specific disease. Termination is the only most effective treatment. Elucidation of the molecular mechanism of PE, and defined new diagnostic markers for PE, are meaningful for the early diagnosis and treatment of PE. Previous studies of the applicant showed that the expression of histone acetyltranseferase CSRP2BP was significantly decreased in placentas of PE patients, and is associated with elevated blood pressure in PE patients. In addition，silencing CSRP2BP down-regulated the expression of FOXA1 and inhibited the proliferation, migration and invasion of human trophoblast derived HTR-8 cells. Based on the above results, the applicant proposed the hypothesis that "CSRP2BP regulates the function of trophoblasts by regulating the expression of FOXA1 and might participate in the occurrence and development of preeclampsia". We plan to silence or overexpress CSRP2BP in human trophoblast HTR-8 cells and human induced pluripotent stem cells. In addition, we will generate trophoblasts conditional knockout mice of CSRP2BP. These three models will be used to study the regulatory effect of CSRP2BP on trophoblasts and its possible mechanism in PE. Meanwhile, the correlation between CSRP2BP and PE will be studied based on clinical cases data. This study is expected to provide new targets for early clinical prediction and treatment of PE.