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Decreased Placental FPR2 in Early Pregnancies That Later Developed Small-For-Gestation Age: A Potential Role of FPR2 in the Regulation of Epithelial-Mesenchymal Transition

We reported earlier that an anti-inflammatory small peptide receptor-formyl peptide receptor-2 (FPR2) was significantly decreased in placentas from third trimester pregnancies complicated with fetal growth restriction (FGR), compared to placentas from uncomplicated control pregnancies, suggesting FP...

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Autores principales: Murthi, Padma, Rajaraman, Gayathri, Erwich, Jan Jaap H.M., Dimitriadis, Evdokia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226808/
https://www.ncbi.nlm.nih.gov/pubmed/32290034
http://dx.doi.org/10.3390/cells9040921
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author Murthi, Padma
Rajaraman, Gayathri
Erwich, Jan Jaap H.M.
Dimitriadis, Evdokia
author_facet Murthi, Padma
Rajaraman, Gayathri
Erwich, Jan Jaap H.M.
Dimitriadis, Evdokia
author_sort Murthi, Padma
collection PubMed
description We reported earlier that an anti-inflammatory small peptide receptor-formyl peptide receptor-2 (FPR2) was significantly decreased in placentas from third trimester pregnancies complicated with fetal growth restriction (FGR), compared to placentas from uncomplicated control pregnancies, suggesting FPR2 may play a role in the development of FGR. The aim of this study is to investigate whether the actions of FPR2 alters placental growth process in humans. Accordingly, using small-for-gestation age (SGA) as a proxy for FGR, we hypothesize that FPR2 expression is decreased in first-trimester placentas of women who later manifest FGR, and contributes to aberrant trophoblast function and the development of FGR. Chorionic villus sampling (CVS) tissues were collected at 10–12 weeks gestation in 70 patients with singleton fetuses; surplus tissue was used. Real-time PCR and immunoassays were performed to quantitate FPR2 gene and protein expression. Silencing of FPR2 was performed in two independent, trophoblast-derived cell lines, HTR-8/SVneo and JEG-3 to investigate the functional consequences of FPR2 gene downregulation. FPR2 mRNA relative to 18S rRNA was significantly decreased in placentae from SGA-pregnancies (n = 28) compared with controls (n = 52) (p < 0.0001). Placental FPR2 protein was significantly decreased in SGA compared with control (n = 10 in each group, p < 0.05). Proliferative, migratory and invasive potential of the human placental-derived cell lines, HTR-8/SVneo and JEG-3 were significantly reduced in siFPR2 treated cells compared with siCONT control groups. Down-stream signaling molecules, STAT5B and SOCS3 were identified as target genes of FPR2 action in the trophoblast-derived cell lines and in SGA and control chorionic villous tissues. FPR2 is a novel regulator of key molecular pathways and functions in placental development, and its decreased expression in women destined to develop FGR reinforces a placental origin of SGA/FGR, and that it contributes to causing the development of SGA/FGR.
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spelling pubmed-72268082020-05-18 Decreased Placental FPR2 in Early Pregnancies That Later Developed Small-For-Gestation Age: A Potential Role of FPR2 in the Regulation of Epithelial-Mesenchymal Transition Murthi, Padma Rajaraman, Gayathri Erwich, Jan Jaap H.M. Dimitriadis, Evdokia Cells Article We reported earlier that an anti-inflammatory small peptide receptor-formyl peptide receptor-2 (FPR2) was significantly decreased in placentas from third trimester pregnancies complicated with fetal growth restriction (FGR), compared to placentas from uncomplicated control pregnancies, suggesting FPR2 may play a role in the development of FGR. The aim of this study is to investigate whether the actions of FPR2 alters placental growth process in humans. Accordingly, using small-for-gestation age (SGA) as a proxy for FGR, we hypothesize that FPR2 expression is decreased in first-trimester placentas of women who later manifest FGR, and contributes to aberrant trophoblast function and the development of FGR. Chorionic villus sampling (CVS) tissues were collected at 10–12 weeks gestation in 70 patients with singleton fetuses; surplus tissue was used. Real-time PCR and immunoassays were performed to quantitate FPR2 gene and protein expression. Silencing of FPR2 was performed in two independent, trophoblast-derived cell lines, HTR-8/SVneo and JEG-3 to investigate the functional consequences of FPR2 gene downregulation. FPR2 mRNA relative to 18S rRNA was significantly decreased in placentae from SGA-pregnancies (n = 28) compared with controls (n = 52) (p < 0.0001). Placental FPR2 protein was significantly decreased in SGA compared with control (n = 10 in each group, p < 0.05). Proliferative, migratory and invasive potential of the human placental-derived cell lines, HTR-8/SVneo and JEG-3 were significantly reduced in siFPR2 treated cells compared with siCONT control groups. Down-stream signaling molecules, STAT5B and SOCS3 were identified as target genes of FPR2 action in the trophoblast-derived cell lines and in SGA and control chorionic villous tissues. FPR2 is a novel regulator of key molecular pathways and functions in placental development, and its decreased expression in women destined to develop FGR reinforces a placental origin of SGA/FGR, and that it contributes to causing the development of SGA/FGR. MDPI 2020-04-10 /pmc/articles/PMC7226808/ /pubmed/32290034 http://dx.doi.org/10.3390/cells9040921 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Murthi, Padma
Rajaraman, Gayathri
Erwich, Jan Jaap H.M.
Dimitriadis, Evdokia
Decreased Placental FPR2 in Early Pregnancies That Later Developed Small-For-Gestation Age: A Potential Role of FPR2 in the Regulation of Epithelial-Mesenchymal Transition
title Decreased Placental FPR2 in Early Pregnancies That Later Developed Small-For-Gestation Age: A Potential Role of FPR2 in the Regulation of Epithelial-Mesenchymal Transition
title_full Decreased Placental FPR2 in Early Pregnancies That Later Developed Small-For-Gestation Age: A Potential Role of FPR2 in the Regulation of Epithelial-Mesenchymal Transition
title_fullStr Decreased Placental FPR2 in Early Pregnancies That Later Developed Small-For-Gestation Age: A Potential Role of FPR2 in the Regulation of Epithelial-Mesenchymal Transition
title_full_unstemmed Decreased Placental FPR2 in Early Pregnancies That Later Developed Small-For-Gestation Age: A Potential Role of FPR2 in the Regulation of Epithelial-Mesenchymal Transition
title_short Decreased Placental FPR2 in Early Pregnancies That Later Developed Small-For-Gestation Age: A Potential Role of FPR2 in the Regulation of Epithelial-Mesenchymal Transition
title_sort decreased placental fpr2 in early pregnancies that later developed small-for-gestation age: a potential role of fpr2 in the regulation of epithelial-mesenchymal transition
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226808/
https://www.ncbi.nlm.nih.gov/pubmed/32290034
http://dx.doi.org/10.3390/cells9040921
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