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MiR-101-containing extracellular vesicles bind to BRD4 and enhance proliferation and migration of trophoblasts in preeclampsia

BACKGROUND: Preeclampsia (PE) is a frequently occurring pregnancy disorder in the placenta, which results in various maternal and fetal complications. The current study aims to evaluate the role of extracellular vesicles (EVs)-encapsulated microRNA (miR)-101 in biological processes of trophoblasts i...

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Detalles Bibliográficos
Autores principales: Cui, Jinhui, Chen, Xinjuan, Lin, Shuo, Li, Ling, Fan, Jianhui, Hou, Hongying, Li, Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291671/
https://www.ncbi.nlm.nih.gov/pubmed/32527308
http://dx.doi.org/10.1186/s13287-020-01720-9
Descripción
Sumario:BACKGROUND: Preeclampsia (PE) is a frequently occurring pregnancy disorder in the placenta, which results in various maternal and fetal complications. The current study aims to evaluate the role of extracellular vesicles (EVs)-encapsulated microRNA (miR)-101 in biological processes of trophoblasts in PE and its underlying mechanism. METHODS: Human umbilical cord mesenchymal stem cell (HUCMSC) and HUCMSC-derived EVs were isolated and cultured, after which EV characterization was carried out using PKH67 staining. In silico analyses were adopted to predict the downstream target genes of miR-101, and dual luciferase reporter gene assay was applied to validate the binding affinity. Furthermore, loss- and gain-of-function approaches were adopted to determine the role of miR-101 and bromodomain-containing protein 4 (BRD4) in trophoblast proliferation and invasion using EDU staining and transwell assay. In addition, a rat model of PE was established to verify the function of EV-encapsulated miR-101 in vivo. RESULTS: Placental tissues obtained from PE patients presented with downregulated miR-101 expression and upregulated BRD4 and CXCL11 expression. EV-encapsulated miR-101 from HUCMSCs could be delivered into the trophoblast HTR-8/SVneo cells, thus enhancing proliferation and migration of trophoblasts. Mechanically, miR-101 targeted and negatively regulated BRD4 expression. BRD4 knockdown promoted the proliferation and migration of trophoblasts by suppressing NF-κB/CXCL11 axis. EV-encapsulated miR-101 from HUCMSCs also reduced blood pressure and 24 h urine protein in vivo, thereby ameliorating PE. CONCLUSION: In summary, EV-encapsulated miR-101 promoted proliferation and migration of placental trophoblasts through the inhibition of BRD4 expression via NF-κB/CXCL11 inactivation.