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Amnion-Derived Mesenchymal Stem Cell Exosomes-Mediated Autophagy Promotes the Survival of Trophoblasts Under Hypoxia Through mTOR Pathway by the Downregulation of EZH2

Human amnion-derived mesenchymal stem cells (AD-MSCs) have been reported as a promising effective treatment to repair tissue. Trophoblast dysfunction during pregnancy is significantly involved in the pathogenesis of preeclampsia (PE). To understand how AD-MSCs regulated trophoblast function, we trea...

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Autores principales: Chu, Yijing, Chen, Weiping, Peng, Wei, Liu, Yong, Xu, Lin, Zuo, Jianxin, Zhou, Jun, Zhang, Yan, Zhang, Ning, Li, Jing, Liu, Ling, Yao, Ke, Gao, Guoqiang, Wang, Xiaofei, Han, Rendong, Liu, Chong, Li, Yan, Zhou, Huansheng, Huang, Yuxiang, Ye, Yuanhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693549/
https://www.ncbi.nlm.nih.gov/pubmed/33304896
http://dx.doi.org/10.3389/fcell.2020.545852
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author Chu, Yijing
Chen, Weiping
Peng, Wei
Liu, Yong
Xu, Lin
Zuo, Jianxin
Zhou, Jun
Zhang, Yan
Zhang, Ning
Li, Jing
Liu, Ling
Yao, Ke
Gao, Guoqiang
Wang, Xiaofei
Han, Rendong
Liu, Chong
Li, Yan
Zhou, Huansheng
Huang, Yuxiang
Ye, Yuanhua
author_facet Chu, Yijing
Chen, Weiping
Peng, Wei
Liu, Yong
Xu, Lin
Zuo, Jianxin
Zhou, Jun
Zhang, Yan
Zhang, Ning
Li, Jing
Liu, Ling
Yao, Ke
Gao, Guoqiang
Wang, Xiaofei
Han, Rendong
Liu, Chong
Li, Yan
Zhou, Huansheng
Huang, Yuxiang
Ye, Yuanhua
author_sort Chu, Yijing
collection PubMed
description Human amnion-derived mesenchymal stem cells (AD-MSCs) have been reported as a promising effective treatment to repair tissue. Trophoblast dysfunction during pregnancy is significantly involved in the pathogenesis of preeclampsia (PE). To understand how AD-MSCs regulated trophoblast function, we treated trophoblasts with AD-MSC-derived exosomes under hypoxic conditions. The treatment markedly enhanced the trophoblast proliferation and autophagy. Furthermore, significant decrease of EZH2 levels and inactivation of mTOR signaling were observed in AD-MSC exosomes-treated trophoblasts. Consistent with these findings, overexpression of EZH2 activated the mTOR signaling in trophoblasts, and reduced the autophagy and survival of trophoblasts, even in the presence of AD-MSC-derived exosomes. In addition, EZH2 inhibition exhibited the same trophoblast autophagy-promoting effect as induced by AD-MSC-derived exosomes, also accompanied by the inactivation of mTOR signaling. Importantly, when EZH2 was overexpressed in trophoblasts treated with PQR620, a specific mTOR signaling inhibitor, the autophagy and proliferation in trophoblasts were decreased. Studies on human placental explants also confirmed our findings by showing that the expression levels of EZH2 and mTOR were decreased while the autophagy-associated protein level was increased by AD-MSC-derived exosome treatment. In summary, our results suggest that EZH2-dependent mTOR signaling inactivation mediated by AD-MSC-derived exosomes is a prerequisite for autophagy augmentation in hypoxic trophoblasts.
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spelling pubmed-76935492020-12-09 Amnion-Derived Mesenchymal Stem Cell Exosomes-Mediated Autophagy Promotes the Survival of Trophoblasts Under Hypoxia Through mTOR Pathway by the Downregulation of EZH2 Chu, Yijing Chen, Weiping Peng, Wei Liu, Yong Xu, Lin Zuo, Jianxin Zhou, Jun Zhang, Yan Zhang, Ning Li, Jing Liu, Ling Yao, Ke Gao, Guoqiang Wang, Xiaofei Han, Rendong Liu, Chong Li, Yan Zhou, Huansheng Huang, Yuxiang Ye, Yuanhua Front Cell Dev Biol Cell and Developmental Biology Human amnion-derived mesenchymal stem cells (AD-MSCs) have been reported as a promising effective treatment to repair tissue. Trophoblast dysfunction during pregnancy is significantly involved in the pathogenesis of preeclampsia (PE). To understand how AD-MSCs regulated trophoblast function, we treated trophoblasts with AD-MSC-derived exosomes under hypoxic conditions. The treatment markedly enhanced the trophoblast proliferation and autophagy. Furthermore, significant decrease of EZH2 levels and inactivation of mTOR signaling were observed in AD-MSC exosomes-treated trophoblasts. Consistent with these findings, overexpression of EZH2 activated the mTOR signaling in trophoblasts, and reduced the autophagy and survival of trophoblasts, even in the presence of AD-MSC-derived exosomes. In addition, EZH2 inhibition exhibited the same trophoblast autophagy-promoting effect as induced by AD-MSC-derived exosomes, also accompanied by the inactivation of mTOR signaling. Importantly, when EZH2 was overexpressed in trophoblasts treated with PQR620, a specific mTOR signaling inhibitor, the autophagy and proliferation in trophoblasts were decreased. Studies on human placental explants also confirmed our findings by showing that the expression levels of EZH2 and mTOR were decreased while the autophagy-associated protein level was increased by AD-MSC-derived exosome treatment. In summary, our results suggest that EZH2-dependent mTOR signaling inactivation mediated by AD-MSC-derived exosomes is a prerequisite for autophagy augmentation in hypoxic trophoblasts. Frontiers Media S.A. 2020-11-11 /pmc/articles/PMC7693549/ /pubmed/33304896 http://dx.doi.org/10.3389/fcell.2020.545852 Text en Copyright © 2020 Chu, Chen, Peng, Liu, Xu, Zuo, Zhou, Zhang, Zhang, Li, Liu, Yao, Gao, Wang, Han, Liu, Li, Zhou, Huang and Ye. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Chu, Yijing
Chen, Weiping
Peng, Wei
Liu, Yong
Xu, Lin
Zuo, Jianxin
Zhou, Jun
Zhang, Yan
Zhang, Ning
Li, Jing
Liu, Ling
Yao, Ke
Gao, Guoqiang
Wang, Xiaofei
Han, Rendong
Liu, Chong
Li, Yan
Zhou, Huansheng
Huang, Yuxiang
Ye, Yuanhua
Amnion-Derived Mesenchymal Stem Cell Exosomes-Mediated Autophagy Promotes the Survival of Trophoblasts Under Hypoxia Through mTOR Pathway by the Downregulation of EZH2
title Amnion-Derived Mesenchymal Stem Cell Exosomes-Mediated Autophagy Promotes the Survival of Trophoblasts Under Hypoxia Through mTOR Pathway by the Downregulation of EZH2
title_full Amnion-Derived Mesenchymal Stem Cell Exosomes-Mediated Autophagy Promotes the Survival of Trophoblasts Under Hypoxia Through mTOR Pathway by the Downregulation of EZH2
title_fullStr Amnion-Derived Mesenchymal Stem Cell Exosomes-Mediated Autophagy Promotes the Survival of Trophoblasts Under Hypoxia Through mTOR Pathway by the Downregulation of EZH2
title_full_unstemmed Amnion-Derived Mesenchymal Stem Cell Exosomes-Mediated Autophagy Promotes the Survival of Trophoblasts Under Hypoxia Through mTOR Pathway by the Downregulation of EZH2
title_short Amnion-Derived Mesenchymal Stem Cell Exosomes-Mediated Autophagy Promotes the Survival of Trophoblasts Under Hypoxia Through mTOR Pathway by the Downregulation of EZH2
title_sort amnion-derived mesenchymal stem cell exosomes-mediated autophagy promotes the survival of trophoblasts under hypoxia through mtor pathway by the downregulation of ezh2
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693549/
https://www.ncbi.nlm.nih.gov/pubmed/33304896
http://dx.doi.org/10.3389/fcell.2020.545852
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