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 

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

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 9 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.637248

DOI=10.3389/fcell.2021.637248

ISSN=2296-634X

ABSTRACT=Premature infants have a high risk of bronchopulmonary dysplasia (BPD) characterized by abnormal development of alveoli and pulmonary vessel. Exosomes and exosomal miRNAs (EXO-miRNAs) from bronchoalveolar lavage fluid were shown to be involved in the development of BPD and might serve as predictive biomarkers. However, the roles of exosomes and EXO-miRNAs derived from umbilical cord blood in the incidence of BPD are yet to be elucidated. In this study, we showed that umbilical cord blood-derived exosomes in BPD group impaired angiogenesis. Next generation sequencing of the exosome RNAs uncovered a total of 418 differentially expressed EXO-miRNAs that were largely enriched in pathways including PI3K/Akt signaling pathway and angiogenesis related signaling pathways. The expression of hsa-miR-103a-3p and hsa-miR-185-5p showed the most significant reduction and hsa-miR-200a-3p was the only miRNA showing increased expression. In addition, we also found that overexpression of hsa-miR-185-5p and hsa-miR-103a-3p in HUVECs significantly enhanced endothelial cell proliferation, tube formation and cell migration; however, overexpressing hsa-miR-200a-3p gave opposite results. Our study demonstrates that exosomes derived from umbilical cord blood of BPD infants could impair angiogenesis, which is potentially mediated by differentially expressed EXO-miRNAs packaged in the exosomes.