Xiaobo 赵肖波 Zhao, Qizhi He, Zhiping Wu, Tao Duan
Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, No. 536, Changle Road, 200040 Shanghai, PR China.
Department of Pathology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, No. 536, Changle Road, 200040 Shanghai, PR China.
Pregnancy Hypertens. 2019 Jan;15:201-208. doi: 10.1016/j.preghy.2019.01.002. Epub 2019 Jan 10.
Endoglin is expressed in human placenta and plays an important role in the pathogenesis of preeclampsia. Dysregulation of microRNAs in placental tissues has been recently suggested to be involved in the pathogenesis of preeclampsia. Until now, few studies have shed light on the correlation between endoglin and microRNAs, the latter of which may regulate the expression of ENG, a gene encoding endoglin, in placenta. In this study, we aim to investigate the regulation of ENG by microRNAs.
We located the microRNAs that might regulate the expression of ENG. Candidate microRNAs were tested if they had an impact on trophoblast function.
We compared endoglin expression between normotensive and preeclamptic placentas by using immunohistochemistry and real-time PCR. Downregulated microRNAs in preeclamptic placenta were revealed from a literature review. A bioinformatics assay was performed to predict those that might target ENG. Real-time PCR, Western blotting and dual luciferase assay were used to verify the targeting. The effects of the microRNAs on trophoblasts were evaluated by transwell invasion assay.
The endoglin level was significantly higher in preeclamptic placenta than in normotensive placenta. ENG was validated as the direct target of miR-149-5p and was inversely correlated with it. MiR-149-5p promoted the invasion of trophoblast cells, and this promotion was abrogated by the overexpression of ENG.
Our findings highlight the importance of miR-149-5p in the pathogenesis of preeclampsia and provide new insight into the development of the disease.
内皮糖蛋白在人胎盘中表达，在子痫前期的发病机制中起重要作用。最近有研究表明，胎盘组织中微小RNA的失调与子痫前期的发病机制有关。到目前为止，很少有研究阐明内皮糖蛋白与微小RNA之间的相关性，其中微小RNA可能调节胎盘内编码内皮糖蛋白的ENG基因的表达。在本研究中，我们旨在研究微小RNA对ENG的调控作用。
我们定位了可能调节ENG表达的微小RNA。测试候选微小RNA对滋养层细胞功能的影响。
我们通过免疫组织化学和实时定量PCR比较了正常血压和子痫前期胎盘之间内皮糖蛋白的表达。通过文献综述揭示子痫前期胎盘中下调的微小RNA。进行生物信息学分析以预测可能靶向ENG的微小RNA。使用实时定量PCR、蛋白质印迹法和双荧光素酶测定法验证靶向作用。通过Transwell侵袭试验评估微小RNA对滋养层细胞的影响。
子痫前期胎盘内皮糖蛋白水平显著高于正常血压胎盘。ENG被验证为miR-149-5p的直接靶点，且与之呈负相关。MiR-149-5p促进滋养层细胞的侵袭，而ENG的过表达消除了这种促进作用。
我们的研究结果突出了miR-149-5p在子痫前期发病机制中的重要性，并为该疾病的发展提供了新的见解。
