Circulating microvesicles miR139-3p from bronchopulmonary dysplasia aggravates pulmonary vascular simplification by targeting 4E binding protein 1

作者全名："Yu, Linchao; He, Rui; Liu, Chan; Shi, Yuan; Wang, Daoxin"

作者地址："[Yu, Linchao; He, Rui; Wang, Daoxin] Chongqing Med Univ, Affiliated Hosp 2, Dept Resp Med, Chongqing, Peoples R China; [Liu, Chan; Shi, Yuan] Chongqing Med Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth & Disorders, Dept Neonatol,Minist Educ,Key Lab Child Dev & Diso, Chongqing, Peoples R China"

通信作者："Wang, DX (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Resp Med, Chongqing, Peoples R China."

来源：JOURNAL OF GENE MEDICINE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001167439600001

JCR分区：Q2

影响因子：3.2

年份：2024

卷号：26

期号：2

开始页：　

结束页：　

文献类型：Article

关键词：bronchopulmonary dysplasia; circulating microvesicles; miR139-3p; vascular simplification

摘要："BackgroundMicrovesicles (MVs) play a crucial role in bronchopulmonary dysplasia (BPD). There are many MVs in circulating plasma, and they are in direct contact with lung endothelial cells. However, the molecular mechanism and causative effect of circulating MVs on BPD remain unclear.MethodsClinical plasma samples were collected, circulating MVs were isolated, and microRNA (miRNA) sequencing was performed. The BPD model was established, and different MVs were administered. Alveoli and pulmonary vessels were examined by hematoxylin-eosin staining, and body weight and length were measured. In vitro, gene expression was disrupted by miRNA mimics, miRNA inhibitors or plasmid transfection. Cell proliferation and protein expression were detected by cell scratch assay, accurate 5-ethynyl-2-deoxyuridine test, western blotting, or immunofluorescence assay.ResultsBPD-derived MVs further aggravated pulmonary vascular simplification, while circulating MVs from control mice mitigated pulmonary vascular simplification. Micro-RNA sequencing and independent sample verification revealed that miR139-3p, but not miR6125 or miR193b-3p, was the most critical effector molecule in MVs. Mechanism studies showed that eukaryotic translation initiation factor 4E binding protein 1 was the target gene for miR139-3p. In addition, we found that supplementation of miR139-3p inhibitor partially alleviated pulmonary vascular simplification.ConclusionsThese results indicate that circulating MVs are involved in forming BPD by carrying miR139-3p molecules and support miR139-3p inhibitors as a potential therapeutic strategy for alleviating pulmonary vascular simplification in BPD. Microvesicles (MVs) derived from bronchopulmonary dysplasia (BPD) show a negative lung simplification role through complex gene networks, and miR139-3p, miR6125 and miR193b-3p are significantly enriched in MVs. Among them, miR139-3p may be the most critical molecule in MVs affecting lung simplification. These findings may facilitate the identification of the role of MVs in the pathological of BPD and the treatment of BPD based on MVs' strategies. image"

基金机构："Natural Science Foundation of Chongqing, China"

基金资助正文：All authors acknowledge Professor Chen for facilitating the initiation of the project. We thank RH and CL for communicating with participants and collecting data.