Circulating exosomal and Argonaute-bound microRNAs in preeclampsia

Orsolya Biró, Ábel Fóthi, Bálint Alasztics, Bálint Nagy, Tamás I. Orbán, J. Rigó

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Introduction: microRNAs (miRNAs) play important role in the regulation of placental development, and abnormal miRNA expression is associated with preeclampsia (PE). miRNAs are released from trophoblast cells to maternal blood flow, where they are highly stable, being encapsulated inside extracellular vesicles, like exosomes or bound to Argonaute proteins. In PE, placental dysfunction leads to aberrant extracellular miRNA secretion. hsa-miR-210 is a hypoxia-sensitive miRNA found to be upregulated in PE; however, it is unknown whether it is the cause or the consequence of the disease. Objective: Our aim was to analyze the expression of several miRNAs, including hsa-miR-210 in placenta, exosome and Ago-bound fractions comparing normal (N) and PE pregnancies. We performed in vitro analyses of extracellular hsa-miR-210 secretion of trophoblast cell cultures (of villous and extravillous origin) under hypoxic condition. Methods: PE and N placenta samples were collected from C-sections, and blood samples were drawn from each pregnant woman in the third trimester. HTR-8 and JAR cell lines were cultured in exosome-free media and treated with hypoxia-mimetic agents. Exosome and Ago-bound fractions were isolated by membrane affinity spin column method from plasma and cell media. Short RNAs were extracted from exosomes and vesicle-free fractions, and total-RNA was isolated from the placenta samples. The RNA purity and concentration were measured by spectrophotometry. Expression analysis was carried out by qPCR with specific primers to target and reference miRNAs. Results: The level of hsa-miR-210 was significantly higher in PE placentas, which could cause a minor increase of exosomal and a high elevation of Ago-bound miR-210 in circulation. Hypoxia lead to intracellular hsa-miR-210 upregulation in trophoblast cell lines. In extravillous cell (HTR-8) media, only the level of exosomal hsa-miR-210 was increased but no change in Ago-bound hsa-miR-210 level was observed. In contrast, in villous cell (JAR) media, the level of exosomal hsa-miR-210 was increased and enhanced release of Ago-bound hsa-miR-210 was also observed. Conclusion: Based on our data, we postulate that in PE, exosomal hsa-miR-210 is secreted actively from the trophoblast, and by intercellular communication, it may have a role in disease etiology. In addition, there is a passive release of Ago-bound hsa-miR-210 into the circulation, which may represent by-products of cell-death and is thereby a possible consequence of the disease.

Original languageEnglish
Pages (from-to)138-144
Number of pages7
JournalGene
Volume692
DOIs
Publication statusPublished - Apr 15 2019

Fingerprint

Pre-Eclampsia
MicroRNAs
Exosomes
Trophoblasts
Placenta
RNA
human MIRN210 microRNA
Argonaute Proteins
Cell Line
Placentation
Spectrophotometry
Third Pregnancy Trimester
Plasma Cells
Pregnant Women
Cell Death
Up-Regulation
Cell Culture Techniques
Mothers
Pregnancy
Membranes

Keywords

  • hsa-miR-210
  • HTR-8
  • JAR
  • Placenta

ASJC Scopus subject areas

  • Genetics

Cite this

Biró, O., Fóthi, Á., Alasztics, B., Nagy, B., Orbán, T. I., & Rigó, J. (2019). Circulating exosomal and Argonaute-bound microRNAs in preeclampsia. Gene, 692, 138-144. https://doi.org/10.1016/j.gene.2019.01.012

Circulating exosomal and Argonaute-bound microRNAs in preeclampsia. / Biró, Orsolya; Fóthi, Ábel; Alasztics, Bálint; Nagy, Bálint; Orbán, Tamás I.; Rigó, J.

In: Gene, Vol. 692, 15.04.2019, p. 138-144.

Research output: Contribution to journalArticle

Biró, O, Fóthi, Á, Alasztics, B, Nagy, B, Orbán, TI & Rigó, J 2019, 'Circulating exosomal and Argonaute-bound microRNAs in preeclampsia', Gene, vol. 692, pp. 138-144. https://doi.org/10.1016/j.gene.2019.01.012
Biró O, Fóthi Á, Alasztics B, Nagy B, Orbán TI, Rigó J. Circulating exosomal and Argonaute-bound microRNAs in preeclampsia. Gene. 2019 Apr 15;692:138-144. https://doi.org/10.1016/j.gene.2019.01.012
Biró, Orsolya ; Fóthi, Ábel ; Alasztics, Bálint ; Nagy, Bálint ; Orbán, Tamás I. ; Rigó, J. / Circulating exosomal and Argonaute-bound microRNAs in preeclampsia. In: Gene. 2019 ; Vol. 692. pp. 138-144.
@article{dff26ba5fca14ad8bd29bfad5efb43b0,
title = "Circulating exosomal and Argonaute-bound microRNAs in preeclampsia",
abstract = "Introduction: microRNAs (miRNAs) play important role in the regulation of placental development, and abnormal miRNA expression is associated with preeclampsia (PE). miRNAs are released from trophoblast cells to maternal blood flow, where they are highly stable, being encapsulated inside extracellular vesicles, like exosomes or bound to Argonaute proteins. In PE, placental dysfunction leads to aberrant extracellular miRNA secretion. hsa-miR-210 is a hypoxia-sensitive miRNA found to be upregulated in PE; however, it is unknown whether it is the cause or the consequence of the disease. Objective: Our aim was to analyze the expression of several miRNAs, including hsa-miR-210 in placenta, exosome and Ago-bound fractions comparing normal (N) and PE pregnancies. We performed in vitro analyses of extracellular hsa-miR-210 secretion of trophoblast cell cultures (of villous and extravillous origin) under hypoxic condition. Methods: PE and N placenta samples were collected from C-sections, and blood samples were drawn from each pregnant woman in the third trimester. HTR-8 and JAR cell lines were cultured in exosome-free media and treated with hypoxia-mimetic agents. Exosome and Ago-bound fractions were isolated by membrane affinity spin column method from plasma and cell media. Short RNAs were extracted from exosomes and vesicle-free fractions, and total-RNA was isolated from the placenta samples. The RNA purity and concentration were measured by spectrophotometry. Expression analysis was carried out by qPCR with specific primers to target and reference miRNAs. Results: The level of hsa-miR-210 was significantly higher in PE placentas, which could cause a minor increase of exosomal and a high elevation of Ago-bound miR-210 in circulation. Hypoxia lead to intracellular hsa-miR-210 upregulation in trophoblast cell lines. In extravillous cell (HTR-8) media, only the level of exosomal hsa-miR-210 was increased but no change in Ago-bound hsa-miR-210 level was observed. In contrast, in villous cell (JAR) media, the level of exosomal hsa-miR-210 was increased and enhanced release of Ago-bound hsa-miR-210 was also observed. Conclusion: Based on our data, we postulate that in PE, exosomal hsa-miR-210 is secreted actively from the trophoblast, and by intercellular communication, it may have a role in disease etiology. In addition, there is a passive release of Ago-bound hsa-miR-210 into the circulation, which may represent by-products of cell-death and is thereby a possible consequence of the disease.",
keywords = "hsa-miR-210, HTR-8, JAR, Placenta",
author = "Orsolya Bir{\'o} and {\'A}bel F{\'o}thi and B{\'a}lint Alasztics and B{\'a}lint Nagy and Orb{\'a}n, {Tam{\'a}s I.} and J. Rig{\'o}",
year = "2019",
month = "4",
day = "15",
doi = "10.1016/j.gene.2019.01.012",
language = "English",
volume = "692",
pages = "138--144",
journal = "Gene",
issn = "0378-1119",
publisher = "Elsevier",

}

TY - JOUR

T1 - Circulating exosomal and Argonaute-bound microRNAs in preeclampsia

AU - Biró, Orsolya

AU - Fóthi, Ábel

AU - Alasztics, Bálint

AU - Nagy, Bálint

AU - Orbán, Tamás I.

AU - Rigó, J.

PY - 2019/4/15

Y1 - 2019/4/15

N2 - Introduction: microRNAs (miRNAs) play important role in the regulation of placental development, and abnormal miRNA expression is associated with preeclampsia (PE). miRNAs are released from trophoblast cells to maternal blood flow, where they are highly stable, being encapsulated inside extracellular vesicles, like exosomes or bound to Argonaute proteins. In PE, placental dysfunction leads to aberrant extracellular miRNA secretion. hsa-miR-210 is a hypoxia-sensitive miRNA found to be upregulated in PE; however, it is unknown whether it is the cause or the consequence of the disease. Objective: Our aim was to analyze the expression of several miRNAs, including hsa-miR-210 in placenta, exosome and Ago-bound fractions comparing normal (N) and PE pregnancies. We performed in vitro analyses of extracellular hsa-miR-210 secretion of trophoblast cell cultures (of villous and extravillous origin) under hypoxic condition. Methods: PE and N placenta samples were collected from C-sections, and blood samples were drawn from each pregnant woman in the third trimester. HTR-8 and JAR cell lines were cultured in exosome-free media and treated with hypoxia-mimetic agents. Exosome and Ago-bound fractions were isolated by membrane affinity spin column method from plasma and cell media. Short RNAs were extracted from exosomes and vesicle-free fractions, and total-RNA was isolated from the placenta samples. The RNA purity and concentration were measured by spectrophotometry. Expression analysis was carried out by qPCR with specific primers to target and reference miRNAs. Results: The level of hsa-miR-210 was significantly higher in PE placentas, which could cause a minor increase of exosomal and a high elevation of Ago-bound miR-210 in circulation. Hypoxia lead to intracellular hsa-miR-210 upregulation in trophoblast cell lines. In extravillous cell (HTR-8) media, only the level of exosomal hsa-miR-210 was increased but no change in Ago-bound hsa-miR-210 level was observed. In contrast, in villous cell (JAR) media, the level of exosomal hsa-miR-210 was increased and enhanced release of Ago-bound hsa-miR-210 was also observed. Conclusion: Based on our data, we postulate that in PE, exosomal hsa-miR-210 is secreted actively from the trophoblast, and by intercellular communication, it may have a role in disease etiology. In addition, there is a passive release of Ago-bound hsa-miR-210 into the circulation, which may represent by-products of cell-death and is thereby a possible consequence of the disease.

AB - Introduction: microRNAs (miRNAs) play important role in the regulation of placental development, and abnormal miRNA expression is associated with preeclampsia (PE). miRNAs are released from trophoblast cells to maternal blood flow, where they are highly stable, being encapsulated inside extracellular vesicles, like exosomes or bound to Argonaute proteins. In PE, placental dysfunction leads to aberrant extracellular miRNA secretion. hsa-miR-210 is a hypoxia-sensitive miRNA found to be upregulated in PE; however, it is unknown whether it is the cause or the consequence of the disease. Objective: Our aim was to analyze the expression of several miRNAs, including hsa-miR-210 in placenta, exosome and Ago-bound fractions comparing normal (N) and PE pregnancies. We performed in vitro analyses of extracellular hsa-miR-210 secretion of trophoblast cell cultures (of villous and extravillous origin) under hypoxic condition. Methods: PE and N placenta samples were collected from C-sections, and blood samples were drawn from each pregnant woman in the third trimester. HTR-8 and JAR cell lines were cultured in exosome-free media and treated with hypoxia-mimetic agents. Exosome and Ago-bound fractions were isolated by membrane affinity spin column method from plasma and cell media. Short RNAs were extracted from exosomes and vesicle-free fractions, and total-RNA was isolated from the placenta samples. The RNA purity and concentration were measured by spectrophotometry. Expression analysis was carried out by qPCR with specific primers to target and reference miRNAs. Results: The level of hsa-miR-210 was significantly higher in PE placentas, which could cause a minor increase of exosomal and a high elevation of Ago-bound miR-210 in circulation. Hypoxia lead to intracellular hsa-miR-210 upregulation in trophoblast cell lines. In extravillous cell (HTR-8) media, only the level of exosomal hsa-miR-210 was increased but no change in Ago-bound hsa-miR-210 level was observed. In contrast, in villous cell (JAR) media, the level of exosomal hsa-miR-210 was increased and enhanced release of Ago-bound hsa-miR-210 was also observed. Conclusion: Based on our data, we postulate that in PE, exosomal hsa-miR-210 is secreted actively from the trophoblast, and by intercellular communication, it may have a role in disease etiology. In addition, there is a passive release of Ago-bound hsa-miR-210 into the circulation, which may represent by-products of cell-death and is thereby a possible consequence of the disease.

KW - hsa-miR-210

KW - HTR-8

KW - JAR

KW - Placenta

UR - http://www.scopus.com/inward/record.url?scp=85060289951&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060289951&partnerID=8YFLogxK

U2 - 10.1016/j.gene.2019.01.012

DO - 10.1016/j.gene.2019.01.012

M3 - Article

VL - 692

SP - 138

EP - 144

JO - Gene

JF - Gene

SN - 0378-1119

ER -