Placental Expression of miR-517a/b and miR-517c Contributes to Trophoblast Dysfunction and Preeclampsia

Preeclampsia is a pregnancy specific hypertensive disease that confers significant maternal and fetal risks. While the exact pathophysiology of preeclampsia is unknown, it is widely accepted that placental dysfunction is mechanistically involved. Recent studies reported aberrant expression of placen...

Full description

Bibliographic Details
Main Authors:	Anton, Lauren, Olarerin-George, Anthony O., Hogenesch, John B., Elovitz, Michal A.
Format:	Online
Language:	English
Published:	Public Library of Science 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370750/

id	pubmed-4370750
recordtype	oai_dc
spelling	pubmed-43707502015-04-04 Placental Expression of miR-517a/b and miR-517c Contributes to Trophoblast Dysfunction and Preeclampsia Anton, Lauren Olarerin-George, Anthony O. Hogenesch, John B. Elovitz, Michal A. Research Article Preeclampsia is a pregnancy specific hypertensive disease that confers significant maternal and fetal risks. While the exact pathophysiology of preeclampsia is unknown, it is widely accepted that placental dysfunction is mechanistically involved. Recent studies reported aberrant expression of placenta-specific microRNAs (miRNAs) in preeclampsia including miR-517a/b and miR-517c. Using placental biopsies from a preeclampsia case-control study, we found increased expression of miR-517a/b in term and preterm preeclampsia vs controls, while, miR-517c was increased only in preterm preeclampsia vs controls. To determine if miR-517a/b and miR-517c are regulated by hypoxia, we treated first trimester primary extravillous trophoblast cells (EVTs) with a hypoxia mimetic and found both were induced. To test for a mechanistic role in placental function, we overexpressed miR-517a/b or miR-517c in EVTs which resulted in decreased trophoblast invasion. Additionally, we found that miR-517a/b and miR-517c overexpression increased expression of the anti-angiogenic protein, sFLT1. The regulation of sFLT1 is mostly unknown, however, TNFSF15, a cytokine involved in FLT1 splicing, was also increased by miR-517a/b and miR-517c in EVTs. In summary, we demonstrate that miR-517a/b and miR-517c contribute to the development of preeclampsia and suggest that these miRNAs play a critical role in regulating trophoblast and placental function. Public Library of Science 2015-03-23 /pmc/articles/PMC4370750/ /pubmed/25799546 http://dx.doi.org/10.1371/journal.pone.0122707 Text en © 2015 Anton et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Anton, Lauren Olarerin-George, Anthony O. Hogenesch, John B. Elovitz, Michal A.
spellingShingle	Anton, Lauren Olarerin-George, Anthony O. Hogenesch, John B. Elovitz, Michal A. Placental Expression of miR-517a/b and miR-517c Contributes to Trophoblast Dysfunction and Preeclampsia
author_facet	Anton, Lauren Olarerin-George, Anthony O. Hogenesch, John B. Elovitz, Michal A.
author_sort	Anton, Lauren
title	Placental Expression of miR-517a/b and miR-517c Contributes to Trophoblast Dysfunction and Preeclampsia
title_short	Placental Expression of miR-517a/b and miR-517c Contributes to Trophoblast Dysfunction and Preeclampsia
title_full	Placental Expression of miR-517a/b and miR-517c Contributes to Trophoblast Dysfunction and Preeclampsia
title_fullStr	Placental Expression of miR-517a/b and miR-517c Contributes to Trophoblast Dysfunction and Preeclampsia
title_full_unstemmed	Placental Expression of miR-517a/b and miR-517c Contributes to Trophoblast Dysfunction and Preeclampsia
title_sort	placental expression of mir-517a/b and mir-517c contributes to trophoblast dysfunction and preeclampsia
description	Preeclampsia is a pregnancy specific hypertensive disease that confers significant maternal and fetal risks. While the exact pathophysiology of preeclampsia is unknown, it is widely accepted that placental dysfunction is mechanistically involved. Recent studies reported aberrant expression of placenta-specific microRNAs (miRNAs) in preeclampsia including miR-517a/b and miR-517c. Using placental biopsies from a preeclampsia case-control study, we found increased expression of miR-517a/b in term and preterm preeclampsia vs controls, while, miR-517c was increased only in preterm preeclampsia vs controls. To determine if miR-517a/b and miR-517c are regulated by hypoxia, we treated first trimester primary extravillous trophoblast cells (EVTs) with a hypoxia mimetic and found both were induced. To test for a mechanistic role in placental function, we overexpressed miR-517a/b or miR-517c in EVTs which resulted in decreased trophoblast invasion. Additionally, we found that miR-517a/b and miR-517c overexpression increased expression of the anti-angiogenic protein, sFLT1. The regulation of sFLT1 is mostly unknown, however, TNFSF15, a cytokine involved in FLT1 splicing, was also increased by miR-517a/b and miR-517c in EVTs. In summary, we demonstrate that miR-517a/b and miR-517c contribute to the development of preeclampsia and suggest that these miRNAs play a critical role in regulating trophoblast and placental function.
publisher	Public Library of Science
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370750/
_version_	1613202483894550528

Placental Expression of miR-517a/b and miR-517c Contributes to Trophoblast Dysfunction and Preeclampsia

Similar Items