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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.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>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-\u03baB\/CXCL11 axis. EV-encapsulated miR-101 from HUCMSCs also reduced blood pressure and 24\u2009h urine protein in vivo, thereby ameliorating PE.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>In summary, EV-encapsulated miR-101 promoted proliferation and migration of placental trophoblasts through the inhibition of BRD4 expression via NF-\u03baB\/CXCL11 inactivation.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s13287-020-01720-9","type":"journal-article","created":{"date-parts":[[2020,6,11]],"date-time":"2020-06-11T18:03:52Z","timestamp":1591898632000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["MiR-101-containing extracellular vesicles bind to BRD4 and enhance proliferation and migration of trophoblasts in preeclampsia"],"prefix":"10.1186","volume":"11","author":[{"given":"Jinhui","family":"Cui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongying","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,6,11]]},"reference":[{"issue":"17","key":"1720_CR1","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1182\/blood-2016-03-705434","volume":"128","author":"S Kohli","year":"2016","unstructured":"Kohli S, Ranjan S, Hoffmann J, Kashif M, Daniel EA, Al-Dabet MM, et al. 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Ethical agreements were obtained from the donors or their relatives by written informed consent. The animal experiments were carried out in strict accordance with the recommendations provided by the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health and was approved by the Animal Care and Use Committee of The Third Affiliated Hospital of Sun Yat-Sen University. Maximum efforts were made to minimize unnecessary distress in the animals.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"231"}}