MiR-101-containing extracellular vesicles bind to BRD4 and enhance proliferation and migration of trophoblasts in preeclampsia
Abstract 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 tropho...
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| Format: | Article |
| Language: | English |
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BMC
2020-06-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | http://link.springer.com/article/10.1186/s13287-020-01720-9 |
| _version_ | 1831717970003361792 |
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| author | Jinhui Cui Xinjuan Chen Shuo Lin Ling Li Jianhui Fan Hongying Hou Ping Li |
| author_facet | Jinhui Cui Xinjuan Chen Shuo Lin Ling Li Jianhui Fan Hongying Hou Ping Li |
| author_sort | Jinhui Cui |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-21T01:08:33Z |
| format | Article |
| id | doaj.art-2b4ebbaab5f64292b5e91861fd3f444d |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-21T01:08:33Z |
| publishDate | 2020-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-2b4ebbaab5f64292b5e91861fd3f444d2022-12-21T19:20:58ZengBMCStem Cell Research & Therapy1757-65122020-06-0111111510.1186/s13287-020-01720-9MiR-101-containing extracellular vesicles bind to BRD4 and enhance proliferation and migration of trophoblasts in preeclampsiaJinhui Cui0Xinjuan Chen1Shuo Lin2Ling Li3Jianhui Fan4Hongying Hou5Ping Li6Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Obstetrics and Gynecology, The Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Endocrinology, The Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Obstetrics and Gynecology, The Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Obstetrics and Gynecology, The Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Obstetrics and Gynecology, The Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Obstetrics and Gynecology, The Third Affiliated Hospital of Sun Yat-Sen UniversityAbstract 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.http://link.springer.com/article/10.1186/s13287-020-01720-9PreeclampsiaExtracellular vesiclesMicroRNA-101Bromodomain-containing 4Nuclear factor-kappa BC-X-C motif chemokine ligand 11 |
| spellingShingle | Jinhui Cui Xinjuan Chen Shuo Lin Ling Li Jianhui Fan Hongying Hou Ping Li MiR-101-containing extracellular vesicles bind to BRD4 and enhance proliferation and migration of trophoblasts in preeclampsia Stem Cell Research & Therapy Preeclampsia Extracellular vesicles MicroRNA-101 Bromodomain-containing 4 Nuclear factor-kappa B C-X-C motif chemokine ligand 11 |
| title | MiR-101-containing extracellular vesicles bind to BRD4 and enhance proliferation and migration of trophoblasts in preeclampsia |
| title_full | MiR-101-containing extracellular vesicles bind to BRD4 and enhance proliferation and migration of trophoblasts in preeclampsia |
| title_fullStr | MiR-101-containing extracellular vesicles bind to BRD4 and enhance proliferation and migration of trophoblasts in preeclampsia |
| title_full_unstemmed | MiR-101-containing extracellular vesicles bind to BRD4 and enhance proliferation and migration of trophoblasts in preeclampsia |
| title_short | MiR-101-containing extracellular vesicles bind to BRD4 and enhance proliferation and migration of trophoblasts in preeclampsia |
| title_sort | mir 101 containing extracellular vesicles bind to brd4 and enhance proliferation and migration of trophoblasts in preeclampsia |
| topic | Preeclampsia Extracellular vesicles MicroRNA-101 Bromodomain-containing 4 Nuclear factor-kappa B C-X-C motif chemokine ligand 11 |
| url | http://link.springer.com/article/10.1186/s13287-020-01720-9 |
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