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

Frontiers in Cell and Developmental Biology

Qin Yan¹  Xiu-hong Li²  Hui-ling Wei³  Jian Gu³  Zi-yan Liang³  Chang-yu Lian³  Chun-hong Jia³  Jing Zheng⁴  Zhuang-gui Chen⁵  Xin-qi Zhong⁶  Qi-liang Cui⁶ 

[1] Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China;Department of Maternal and Child Health, School of Public Health, Sun Yat-sen University, Guangzhou, China;Department of Neonatology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China;Department of Obstetrics and Gynecology, University of Wisconsin–Madison, Madison, WI, United States;Department of Pediatrics and Department of Allergy, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, China;

关键词: bronchopulmonary dysplasia;    microRNA;    angiogenesis;    exosome;    preterm infants;   

DOI  :  10.3389/fcell.2021.637248

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown