Chorionic villus-derived mesenchymal stem cell-mediated NRG1 upregulation promotes HTR-8/SVneo cells proliferation through the activation of the NF-κB signaling pathway

In a prior study, our group found that chorionic villus-derived mesenchymal stem cells (CV-MSCs) were capable of promoting trophoblast proliferative and invasive activity. The mechanistic basis for this activity, however, has yet to be clarified. As such, an RNA-Seq analysis was conducted using trop...

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Main Authors: Yajun Liu, Ning Zhang, Yuting Wang, Jianxin Zuo, Jing Wang, Yijing Chu, Yuanhua Ye
Format: Article
Language:English
Published: Elsevier 2023-08-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844023054531
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author Yajun Liu
Ning Zhang
Yuting Wang
Jianxin Zuo
Jing Wang
Yijing Chu
Yuanhua Ye
author_facet Yajun Liu
Ning Zhang
Yuting Wang
Jianxin Zuo
Jing Wang
Yijing Chu
Yuanhua Ye
author_sort Yajun Liu
collection DOAJ
description In a prior study, our group found that chorionic villus-derived mesenchymal stem cells (CV-MSCs) were capable of promoting trophoblast proliferative and invasive activity. The mechanistic basis for this activity, however, has yet to be clarified. As such, an RNA-Seq analysis was conducted using trophoblasts that were treated with or without CV-MSC-conditioned media. Of the differentially expressed genes identified when comparing these two groups of cells, 23 proliferation-associated genes were identified and knocked down to test their functional roles in trophoblasts. These analyses revealed that inhibiting neuregulin 1 (NRG1) expression was sufficient to suppress proliferation and induce cell cycle arrest in trophoblasts. Placental samples from patients with preeclampsia exhibited significantly increased NRG1 expression relative to samples from healthy pregnancies. Following treatment with CV-MSC-conditioned media, NRG1 was upregulated in trophoblasts at the mRNA and protein levels. Relative to control trophoblasts, those in which NRG1 had been knocked down exhibited significantly impaired proliferation and DNA replication with the inactivation of the NF-κB signaling pathway. In contrast, overexpressing NRG1 yielded the opposite trophoblast phenotypes. Even in cells overexpressing NRG1, inhibition of NF-κB signaling was sufficient to significantly suppress trophoblast proliferation (P < 0.05). These results indicate that elevated NRG1 expression may play a role in the ability of CV-MSCs to induce proliferative activity in trophoblasts through the NF-κB signaling axis.
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spelling doaj.art-89e89d847e3a4b1eb7bd791cf9589abd2023-08-30T05:50:59ZengElsevierHeliyon2405-84402023-08-0198e18245Chorionic villus-derived mesenchymal stem cell-mediated NRG1 upregulation promotes HTR-8/SVneo cells proliferation through the activation of the NF-κB signaling pathwayYajun Liu0Ning Zhang1Yuting Wang2Jianxin Zuo3Jing Wang4Yijing Chu5Yuanhua Ye6Department of Obstetrics, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Obstetrics, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Obstetrics, Qingdao Women and Children's Hospital, Qingdao, ChinaDepartment of Obstetrics, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Obstetrics, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Obstetrics, The Affiliated Hospital of Qingdao University, Qingdao, China; Corresponding author. Department of Obstetrics, The Affiliated Hospital of Qingdao University, Qingdao, China.Department of Obstetrics, The Affiliated Hospital of Qingdao University, Qingdao, China; Corresponding author.In a prior study, our group found that chorionic villus-derived mesenchymal stem cells (CV-MSCs) were capable of promoting trophoblast proliferative and invasive activity. The mechanistic basis for this activity, however, has yet to be clarified. As such, an RNA-Seq analysis was conducted using trophoblasts that were treated with or without CV-MSC-conditioned media. Of the differentially expressed genes identified when comparing these two groups of cells, 23 proliferation-associated genes were identified and knocked down to test their functional roles in trophoblasts. These analyses revealed that inhibiting neuregulin 1 (NRG1) expression was sufficient to suppress proliferation and induce cell cycle arrest in trophoblasts. Placental samples from patients with preeclampsia exhibited significantly increased NRG1 expression relative to samples from healthy pregnancies. Following treatment with CV-MSC-conditioned media, NRG1 was upregulated in trophoblasts at the mRNA and protein levels. Relative to control trophoblasts, those in which NRG1 had been knocked down exhibited significantly impaired proliferation and DNA replication with the inactivation of the NF-κB signaling pathway. In contrast, overexpressing NRG1 yielded the opposite trophoblast phenotypes. Even in cells overexpressing NRG1, inhibition of NF-κB signaling was sufficient to significantly suppress trophoblast proliferation (P < 0.05). These results indicate that elevated NRG1 expression may play a role in the ability of CV-MSCs to induce proliferative activity in trophoblasts through the NF-κB signaling axis.http://www.sciencedirect.com/science/article/pii/S2405844023054531Chorionic villus-derived mesenchymal stem cellsTrophoblastsNRG1NF-κB
spellingShingle Yajun Liu
Ning Zhang
Yuting Wang
Jianxin Zuo
Jing Wang
Yijing Chu
Yuanhua Ye
Chorionic villus-derived mesenchymal stem cell-mediated NRG1 upregulation promotes HTR-8/SVneo cells proliferation through the activation of the NF-κB signaling pathway
Heliyon
Chorionic villus-derived mesenchymal stem cells
Trophoblasts
NRG1
NF-κB
title Chorionic villus-derived mesenchymal stem cell-mediated NRG1 upregulation promotes HTR-8/SVneo cells proliferation through the activation of the NF-κB signaling pathway
title_full Chorionic villus-derived mesenchymal stem cell-mediated NRG1 upregulation promotes HTR-8/SVneo cells proliferation through the activation of the NF-κB signaling pathway
title_fullStr Chorionic villus-derived mesenchymal stem cell-mediated NRG1 upregulation promotes HTR-8/SVneo cells proliferation through the activation of the NF-κB signaling pathway
title_full_unstemmed Chorionic villus-derived mesenchymal stem cell-mediated NRG1 upregulation promotes HTR-8/SVneo cells proliferation through the activation of the NF-κB signaling pathway
title_short Chorionic villus-derived mesenchymal stem cell-mediated NRG1 upregulation promotes HTR-8/SVneo cells proliferation through the activation of the NF-κB signaling pathway
title_sort chorionic villus derived mesenchymal stem cell mediated nrg1 upregulation promotes htr 8 svneo cells proliferation through the activation of the nf κb signaling pathway
topic Chorionic villus-derived mesenchymal stem cells
Trophoblasts
NRG1
NF-κB
url http://www.sciencedirect.com/science/article/pii/S2405844023054531
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