Department of Gynecology and Obstetrics, The Second Hospital of Shanxi Medical University, No. 382 Wuyi Road, Taiyuan 030001, Shanxi Province, PR China.
Department of Gynecology and Obstetrics, The Second Hospital of Shanxi Medical University, No. 382 Wuyi Road, Taiyuan 030001, Shanxi Province, PR China.
Biomed Pharmacother. 2019 Jul;115:108953. doi: 10.1016/j.biopha.2019.108953. Epub 2019 May 7.
Preeclampsia is a pregnancy-specific syndrome characterized by hypertension and proteinuria. Impaired trophoblast invasion partly modulated by abnormal MAPK1/ERK2 signaling played important roles in the pathological process of preeclampsia. The objective of this study is to investigate miR-141-5p regulate ATF2 via effecting MAPK1/ERK2 signaling to promote preeclampsia.
The maternal placentae and clinical data of 30 patients with preeclampsia and 30 healthy pregnant women were collected in the Second Hospital of Shanxi Medical University from July 2015 to April 2016. Transcriptional levels of miR-141-5p in placentae were monitored using quantitative real-time reverse transcription-polymerase chain reaction. The target gene of miR-141-5p was analyzed with "TargetScanHuman Release 7.2″. To evaluate the pathways of this response, MAPK1 and ERK1/2 in placentae were detected using immunohistochemistry and Western Blot. Transfection experiment was used to verify the function of miR-141-5p regulating ATF2 to effect MAPK1/ERK2 signaling in JEG-3 cells.
miR-141-5p was significantly down-regulated in placentae of patients with preeclampsia, in comparison to the healthy pregnant women groups. There was no difference in MAPK1 expression between placentae of patients with preeclampsia and healthy pregnant women groups. While p-MAPK1 expression was lower in preeclampsia placentae, in comparison to the healthy pregnant women groups. Moreover, inhibition and activation experiments also validate the function of miR-141-5p in effecting p-MAPK1 level in JEG-3 cells. Bioinformatic analysis identified that ATF2 was a target gene of miR-141-5p, which was one DNA-binding protein to effect phosphatase DUSP1 transcription. DUSP1 effect MAPK1/ERK2 signaling in preeclampsia.
miR-141-5p up-regulated transcription factor ATF2 to promote phosphatase DUSP1 expression. DUSP1 expression reduces p-MAPK1 and ERK1/2 expression to promote preeclampsia.
子痫前期是一种妊娠特异性综合征，其特征为高血压和蛋白尿。滋养细胞侵袭受损部分由异常 MAPK1/ERK2 信号调节，在子痫前期的病理过程中发挥重要作用。本研究旨在探讨 miR-141-5p 通过影响 MAPK1/ERK2 信号来调节 ATF2，从而促进子痫前期。
本研究收集了 2015 年 7 月至 2016 年 4 月山西医科大学第二医院 30 例子痫前期患者和 30 例健康孕妇的母体胎盘及临床资料。采用实时定量逆转录聚合酶链反应监测胎盘 miR-141-5p 的转录水平。采用“TargetScanHuman Release 7.2”分析 miR-141-5p 的靶基因。通过免疫组织化学和 Western blot 检测胎盘 MAPK1 和 ERK1/2 来评估该反应的途径。转染实验用于验证 miR-141-5p 调节 ATF2 以影响 JEG-3 细胞中 MAPK1/ERK2 信号的功能。
与健康孕妇组相比，子痫前期患者胎盘 miR-141-5p 表达明显下调。MAPK1 在子痫前期患者胎盘和健康孕妇胎盘之间的表达无差异。而 p-MAPK1 在子痫前期患者胎盘中的表达较低。此外，抑制和激活实验也验证了 miR-141-5p 对 JEG-3 细胞中 p-MAPK1 水平的影响作用。生物信息学分析表明，ATF2 是 miR-141-5p 的靶基因，是一种影响磷酸酶 DUSP1 转录的 DNA 结合蛋白。DUSP1 影响 MAPK1/ERK2 信号在子痫前期中的作用。
miR-141-5p 上调转录因子 ATF2 以促进磷酸酶 DUSP1 的表达。DUSP1 表达降低 p-MAPK1 和 ERK1/2 的表达，从而促进子痫前期。
