miR-141-5p regulate ATF2 via effecting MAPK1/ERK2 signaling to promote preeclampsia

Abstract

Objective: 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.

Study design: 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.

Results: 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.

Conclusion: 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.

Keywords: MAPK(1)/ERK2 pathway; Preeclampsia; miR-141-5p.