Mesenchymal stem cell-derived extracellular vesicles prevent the formation of pulmonary arterial hypertension through a microRNA-200b-dependent mechanism
Abstract Background Bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) have been highly studied with their critical roles as carriers of therapeutic targets such as microRNAs (miRNAs) in the treatment of human diseases, including pulmonary arterial hypertension (PAH). Herein...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | Respiratory Research |
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| Online Access: | https://doi.org/10.1186/s12931-023-02474-7 |
| _version_ | 1797556937281241088 |
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| author | Mengzhi Wan Caiju Lu Yu Liu Feng Luo Jing Zhou Fei Xu |
| author_facet | Mengzhi Wan Caiju Lu Yu Liu Feng Luo Jing Zhou Fei Xu |
| author_sort | Mengzhi Wan |
| collection | DOAJ |
| description | Abstract Background Bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) have been highly studied with their critical roles as carriers of therapeutic targets such as microRNAs (miRNAs) in the treatment of human diseases, including pulmonary arterial hypertension (PAH). Herein, we tried to study the potential of BMSC-EVs to deliver miR-200b for the regulation of macrophage polarization in PAH. Methods Rat models of PAH were induced with monocrotaline treatment, followed by miR-200b expression detection in lung tissues, pulmonary artery smooth muscle cells (PASMCs) and macrophages. miR-200b-containing BMSCs or miR-200b-deficient BMSCs were selected to extract EVs. Then, we assessed the changes in rats with PAH-associated disorders as well as in vitro macrophage polarization and the functions of PASMCs after treatment with BMSC-EVs. Moreover, the interaction between miR-200b, phosphodiesterase 1 A (PDE1A) was identified with a luciferase assay, followed by an exploration of the downstream pathway, cAMP-dependent protein kinase (PKA). Results miR-200b was reduced in lung tissues, PASMCs and macrophages of rats with PAH-like pathology. BMSC-EVs transferred miR-200b into macrophages, and subsequently accelerated their switch to the M2 phenotype and reversed the PAH-associated disorders. Furthermore, miR-200b carried by BMSC-EVs induced PKA phosphorylation by targeting PDE1A, thereby expediting macrophage polarization. Conclusion Our current study highlighted the inhibitory role of BMSC-EV-miR-200b in PAH formation. |
| first_indexed | 2024-03-10T17:10:14Z |
| format | Article |
| id | doaj.art-889d4e02780f419eac8597ad4cf5e411 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-03-10T17:10:14Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-889d4e02780f419eac8597ad4cf5e4112023-11-20T10:40:46ZengBMCRespiratory Research1465-993X2023-09-0124111710.1186/s12931-023-02474-7Mesenchymal stem cell-derived extracellular vesicles prevent the formation of pulmonary arterial hypertension through a microRNA-200b-dependent mechanismMengzhi Wan0Caiju Lu1Yu Liu2Feng Luo3Jing Zhou4Fei Xu5Department of Respiratory Emergency and Critical Care, The First Affiliated Hospital of Nanchang UniversityDepartment of Respiratory Emergency and Critical Care, The First Affiliated Hospital of Nanchang UniversityDepartment of Respiratory Emergency and Critical Care, The First Affiliated Hospital of Nanchang UniversityDepartment of Respiratory Emergency and Critical Care, The First Affiliated Hospital of Nanchang UniversityDepartment of Respiratory Emergency and Critical Care, The First Affiliated Hospital of Nanchang UniversityDepartment of Respiratory Emergency and Critical Care, The First Affiliated Hospital of Nanchang UniversityAbstract Background Bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) have been highly studied with their critical roles as carriers of therapeutic targets such as microRNAs (miRNAs) in the treatment of human diseases, including pulmonary arterial hypertension (PAH). Herein, we tried to study the potential of BMSC-EVs to deliver miR-200b for the regulation of macrophage polarization in PAH. Methods Rat models of PAH were induced with monocrotaline treatment, followed by miR-200b expression detection in lung tissues, pulmonary artery smooth muscle cells (PASMCs) and macrophages. miR-200b-containing BMSCs or miR-200b-deficient BMSCs were selected to extract EVs. Then, we assessed the changes in rats with PAH-associated disorders as well as in vitro macrophage polarization and the functions of PASMCs after treatment with BMSC-EVs. Moreover, the interaction between miR-200b, phosphodiesterase 1 A (PDE1A) was identified with a luciferase assay, followed by an exploration of the downstream pathway, cAMP-dependent protein kinase (PKA). Results miR-200b was reduced in lung tissues, PASMCs and macrophages of rats with PAH-like pathology. BMSC-EVs transferred miR-200b into macrophages, and subsequently accelerated their switch to the M2 phenotype and reversed the PAH-associated disorders. Furthermore, miR-200b carried by BMSC-EVs induced PKA phosphorylation by targeting PDE1A, thereby expediting macrophage polarization. Conclusion Our current study highlighted the inhibitory role of BMSC-EV-miR-200b in PAH formation.https://doi.org/10.1186/s12931-023-02474-7Extracellular vesiclesBone marrow mesenchymal stem cellsPulmonary arterial hypertensionmicroRNA-200bMacrophage polarizationLuciferase |
| spellingShingle | Mengzhi Wan Caiju Lu Yu Liu Feng Luo Jing Zhou Fei Xu Mesenchymal stem cell-derived extracellular vesicles prevent the formation of pulmonary arterial hypertension through a microRNA-200b-dependent mechanism Respiratory Research Extracellular vesicles Bone marrow mesenchymal stem cells Pulmonary arterial hypertension microRNA-200b Macrophage polarization Luciferase |
| title | Mesenchymal stem cell-derived extracellular vesicles prevent the formation of pulmonary arterial hypertension through a microRNA-200b-dependent mechanism |
| title_full | Mesenchymal stem cell-derived extracellular vesicles prevent the formation of pulmonary arterial hypertension through a microRNA-200b-dependent mechanism |
| title_fullStr | Mesenchymal stem cell-derived extracellular vesicles prevent the formation of pulmonary arterial hypertension through a microRNA-200b-dependent mechanism |
| title_full_unstemmed | Mesenchymal stem cell-derived extracellular vesicles prevent the formation of pulmonary arterial hypertension through a microRNA-200b-dependent mechanism |
| title_short | Mesenchymal stem cell-derived extracellular vesicles prevent the formation of pulmonary arterial hypertension through a microRNA-200b-dependent mechanism |
| title_sort | mesenchymal stem cell derived extracellular vesicles prevent the formation of pulmonary arterial hypertension through a microrna 200b dependent mechanism |
| topic | Extracellular vesicles Bone marrow mesenchymal stem cells Pulmonary arterial hypertension microRNA-200b Macrophage polarization Luciferase |
| url | https://doi.org/10.1186/s12931-023-02474-7 |
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