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Umbilical Cord Blood-Derived Exosomes From Very Preterm Infants With Bronchopulmonary Dysplasia Impaired Endothelial Angiogenesis: Roles of Exosomal MicroRNAs

Premature infants have a high risk of bronchopulmonary dysplasia (BPD), which is characterized by abnormal development of alveoli and pulmonary vessels. Exosomes and exosomal miRNAs (EXO-miRNAs) from bronchoalveolar lavage fluid are involved in the development of BPD and might serve as predictive bi...

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Autores principales: Zhong, Xin-qi, Yan, Qin, Chen, Zhuang-gui, Jia, Chun-hong, Li, Xiu-hong, Liang, Zi-yan, Gu, Jian, Wei, Hui-ling, Lian, Chang-yu, Zheng, Jing, Cui, Qi-liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027316/
https://www.ncbi.nlm.nih.gov/pubmed/33842462
http://dx.doi.org/10.3389/fcell.2021.637248
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author Zhong, Xin-qi
Yan, Qin
Chen, Zhuang-gui
Jia, Chun-hong
Li, Xiu-hong
Liang, Zi-yan
Gu, Jian
Wei, Hui-ling
Lian, Chang-yu
Zheng, Jing
Cui, Qi-liang
author_facet Zhong, Xin-qi
Yan, Qin
Chen, Zhuang-gui
Jia, Chun-hong
Li, Xiu-hong
Liang, Zi-yan
Gu, Jian
Wei, Hui-ling
Lian, Chang-yu
Zheng, Jing
Cui, Qi-liang
author_sort Zhong, Xin-qi
collection PubMed
description Premature infants have a high risk of bronchopulmonary dysplasia (BPD), which is characterized by abnormal development of alveoli and pulmonary vessels. Exosomes and exosomal miRNAs (EXO-miRNAs) from bronchoalveolar lavage fluid are involved in the development of BPD and might serve as predictive biomarkers for BPD. However, the roles of exosomes and EXO-miRNAs from umbilical cord blood of BPD infants in regulating angiogenesis are yet to be elucidated. In this study, we showed that umbilical cord blood-derived exosomes from BPD infants impaired angiogenesis in vitro. Next-generation sequencing of EXO-miRNAs from preterm infants without (NBPD group) or with BPD (BPD group) uncovered a total of 418 differentially expressed (DE) EXO-miRNAs. These DE EXO-miRNAs were primarily enriched in cellular function-associated pathways including the PI3K/Akt and angiogenesis-related signaling pathways. Among those EXO-miRNAs which are associated with PI3K/Akt and angiogenesis-related signaling pathways, BPD reduced the expression of hsa-miR-103a-3p and hsa-miR-185-5p exhibiting the most significant reduction (14.3% and 23.1% of NBPD group, respectively); BPD increased hsa-miR-200a-3p expression by 2.64 folds of the NBPD group. Furthermore, overexpression of hsa-miR-103a-3p and hsa-miR-185-5p in normal human umbilical vein endothelial cells (HUVECs) significantly enhanced endothelial cell proliferation, tube formation, and cell migration, whereas overexpressing hsa-miR-200a-3p inhibited these cellular responses. This study demonstrates that exosomes derived from umbilical cord blood of BPD infants impair angiogenesis, possibly via DE EXO-miRNAs, which might contribute to the development of BPD.
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spelling pubmed-80273162021-04-09 Umbilical Cord Blood-Derived Exosomes From Very Preterm Infants With Bronchopulmonary Dysplasia Impaired Endothelial Angiogenesis: Roles of Exosomal MicroRNAs Zhong, Xin-qi Yan, Qin Chen, Zhuang-gui Jia, Chun-hong Li, Xiu-hong Liang, Zi-yan Gu, Jian Wei, Hui-ling Lian, Chang-yu Zheng, Jing Cui, Qi-liang Front Cell Dev Biol Cell and Developmental Biology Premature infants have a high risk of bronchopulmonary dysplasia (BPD), which is characterized by abnormal development of alveoli and pulmonary vessels. Exosomes and exosomal miRNAs (EXO-miRNAs) from bronchoalveolar lavage fluid are involved in the development of BPD and might serve as predictive biomarkers for BPD. However, the roles of exosomes and EXO-miRNAs from umbilical cord blood of BPD infants in regulating angiogenesis are yet to be elucidated. In this study, we showed that umbilical cord blood-derived exosomes from BPD infants impaired angiogenesis in vitro. Next-generation sequencing of EXO-miRNAs from preterm infants without (NBPD group) or with BPD (BPD group) uncovered a total of 418 differentially expressed (DE) EXO-miRNAs. These DE EXO-miRNAs were primarily enriched in cellular function-associated pathways including the PI3K/Akt and angiogenesis-related signaling pathways. Among those EXO-miRNAs which are associated with PI3K/Akt and angiogenesis-related signaling pathways, BPD reduced the expression of hsa-miR-103a-3p and hsa-miR-185-5p exhibiting the most significant reduction (14.3% and 23.1% of NBPD group, respectively); BPD increased hsa-miR-200a-3p expression by 2.64 folds of the NBPD group. Furthermore, overexpression of hsa-miR-103a-3p and hsa-miR-185-5p in normal human umbilical vein endothelial cells (HUVECs) significantly enhanced endothelial cell proliferation, tube formation, and cell migration, whereas overexpressing hsa-miR-200a-3p inhibited these cellular responses. This study demonstrates that exosomes derived from umbilical cord blood of BPD infants impair angiogenesis, possibly via DE EXO-miRNAs, which might contribute to the development of BPD. Frontiers Media S.A. 2021-03-25 /pmc/articles/PMC8027316/ /pubmed/33842462 http://dx.doi.org/10.3389/fcell.2021.637248 Text en Copyright © 2021 Zhong, Yan, Chen, Jia, Li, Liang, Gu, Wei, Lian, Zheng and Cui. https://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
Zhong, Xin-qi
Yan, Qin
Chen, Zhuang-gui
Jia, Chun-hong
Li, Xiu-hong
Liang, Zi-yan
Gu, Jian
Wei, Hui-ling
Lian, Chang-yu
Zheng, Jing
Cui, Qi-liang
Umbilical Cord Blood-Derived Exosomes From Very Preterm Infants With Bronchopulmonary Dysplasia Impaired Endothelial Angiogenesis: Roles of Exosomal MicroRNAs
title Umbilical Cord Blood-Derived Exosomes From Very Preterm Infants With Bronchopulmonary Dysplasia Impaired Endothelial Angiogenesis: Roles of Exosomal MicroRNAs
title_full Umbilical Cord Blood-Derived Exosomes From Very Preterm Infants With Bronchopulmonary Dysplasia Impaired Endothelial Angiogenesis: Roles of Exosomal MicroRNAs
title_fullStr Umbilical Cord Blood-Derived Exosomes From Very Preterm Infants With Bronchopulmonary Dysplasia Impaired Endothelial Angiogenesis: Roles of Exosomal MicroRNAs
title_full_unstemmed Umbilical Cord Blood-Derived Exosomes From Very Preterm Infants With Bronchopulmonary Dysplasia Impaired Endothelial Angiogenesis: Roles of Exosomal MicroRNAs
title_short Umbilical Cord Blood-Derived Exosomes From Very Preterm Infants With Bronchopulmonary Dysplasia Impaired Endothelial Angiogenesis: Roles of Exosomal MicroRNAs
title_sort umbilical cord blood-derived exosomes from very preterm infants with bronchopulmonary dysplasia impaired endothelial angiogenesis: roles of exosomal micrornas
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027316/
https://www.ncbi.nlm.nih.gov/pubmed/33842462
http://dx.doi.org/10.3389/fcell.2021.637248
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