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Down-regulated miR-149-5p contributes to preeclampsia via modulating endoglin expression

机译:下调MiR-149-5P通过调制内痛林表达来贡献前普拉姆裔

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ABSTRACT Objective: 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. Study design: We located the microRNAs that might regulate the expression of ENG. Candidate microRNAs were tested if they had an impact on trophoblast function. Main outcome measures: 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. Results: 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. Conclusions: Our findings highlight the importance of miR-149-5p in the pathogenesis of preeclampsia and provide new insight into the development of the disease.
机译:摘要目的:endoglan在人体胎盘中表达,并在预坦克斯的发病机制中发挥着重要作用。最近提出了胎盘组织中微小ROREORACURACURATION涉及预坦克敏的发病机制。到目前为止,很少有研究揭示了内诺曲板和微大稻草之间的相关性,其后者可以调节胎盘中的ENG,一种编码的腹膜内的基因的表达。在这项研究中,我们的目标是调查MicroRNA的调节。研究设计:我们位于可能调节ENG表达的MicroRNA。如果它们对滋养管功能产生影响,则测试候选微大罗氏。主要观察指标:通过使用免疫组织化学和实时PCR比较了正常血压和牙槌胎盘之间的内阴光表达。从文献综述中揭示了牙槌胎盘中的下调的微小RNA。进行生物信息学测定以预测可能瞄准ENG的人。使用实时PCR,Western印迹和双荧光素酶测定来验证靶向。通过Transwell Invasion测定评估MicroRNA对滋养细胞的影响。结果:前粘土层的胎盘在胎儿胎盘上显着高于标准胎盘。 ENG被验证为MIR-149-5P的直接目标,与IT相反。 MiR-149-5P促进滋养细胞的侵袭,并且通过ENG的过度表达出现这种促进。结论:我们的研究结果突出了MiR-149-5P在预坦克西亚发病机制中的重要性,并为疾病发展提供了新的洞察力。

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