Mesenchymal stem cell-derived exosomal microRNA-182-5p alleviates myocardial ischemia/reperfusion injury by targeting GSDMD in mice
Abstract Recent evidence indicates that exosomes derived from mesenchymal stem cells (MSCs) confer protective effects against myocardial ischemia/reperfusion (I/R) injury. Exosomes are carriers of potentially protective endogenous molecules, including microRNAs (miRNAs/miRs). The current study set o...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-04-01
|
| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-022-00909-6 |
| _version_ | 1818021861548621824 |
|---|---|
| author | Rongchuan Yue Shengzhong Lu Yu Luo Jing Zeng Hao Liang Dan Qin Xiaobo Wang Tao Wang Jun Pu Houxiang Hu |
| author_facet | Rongchuan Yue Shengzhong Lu Yu Luo Jing Zeng Hao Liang Dan Qin Xiaobo Wang Tao Wang Jun Pu Houxiang Hu |
| author_sort | Rongchuan Yue |
| collection | DOAJ |
| description | Abstract Recent evidence indicates that exosomes derived from mesenchymal stem cells (MSCs) confer protective effects against myocardial ischemia/reperfusion (I/R) injury. Exosomes are carriers of potentially protective endogenous molecules, including microRNAs (miRNAs/miRs). The current study set out to test the effects of transferring miR-182-5p from MSC-derived exosomes into myocardial cells on myocardial I/R injury. First, an I/R mouse model was developed by left anterior descending coronary artery occlusion, and myocardial cells were exposed to hypoxia/reoxygenation (H/R) for in vitro I/R model establishment. Loss- and gain-of-function experiments of miR-182-5p and GSDMD were conducted to explore the effects of miR-182-5p via MSC-derived exosomes on cell pyroptosis and viability. GSDMD was robustly expressed in I/R-injured myocardial tissues and H/R-exposed myocardial cells. GSDMD upregulation promoted H/R-induced myocardial cell pyroptosis and reduced viability, corresponding to increased lactate dehydrogenase release, reactive oxygen species production, and pyroptosis. A luciferase assay demonstrated GSDMD as a target of miR-182-5p. In addition, exosomal miR-182-5p was found to diminish GSDMD-dependent cell pyroptosis and inflammation induced by H/R. Furthermore, MSC-derived exosomes carrying miR-182-5p improved cardiac function and reduced myocardial infarction, accompanied with reduced inflammation and cell pyroptosis in vivo. Taken together, our findings suggest a cardioprotective effect of exosomal miR-182-5p against myocardial I/R injury, shedding light on an attractive therapeutic strategy. |
| first_indexed | 2024-04-14T08:24:50Z |
| format | Article |
| id | doaj.art-038dd7ba870c42babaebcdfa031a1ce7 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-04-14T08:24:50Z |
| publishDate | 2022-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-038dd7ba870c42babaebcdfa031a1ce72022-12-22T02:04:06ZengNature Publishing GroupCell Death Discovery2058-77162022-04-018111410.1038/s41420-022-00909-6Mesenchymal stem cell-derived exosomal microRNA-182-5p alleviates myocardial ischemia/reperfusion injury by targeting GSDMD in miceRongchuan Yue0Shengzhong Lu1Yu Luo2Jing Zeng3Hao Liang4Dan Qin5Xiaobo Wang6Tao Wang7Jun Pu8Houxiang Hu9Department of Cardiology, Affiliated Hospital of North Sichuan Medical CollegeDepartment of Cardiology, Affiliated Hospital of North Sichuan Medical CollegeCSCSD, Affiliated Hospital of North Sichuan Medical CollegeDepartment of Cardiology, Affiliated Hospital of North Sichuan Medical CollegeDepartment of Cardiology, Affiliated Hospital of North Sichuan Medical CollegeDepartment of Cardiology, Affiliated Hospital of North Sichuan Medical CollegeDepartment of Cardiology, Affiliated Hospital of North Sichuan Medical CollegeDepartment of Respiratory and Critical Care Medicine, University of Chinese Academy of Sciences Shenzhen HospitalDepartment of Cardiology, Affiliated Hospital of North Sichuan Medical CollegeDepartment of Cardiology, Affiliated Hospital of North Sichuan Medical CollegeAbstract Recent evidence indicates that exosomes derived from mesenchymal stem cells (MSCs) confer protective effects against myocardial ischemia/reperfusion (I/R) injury. Exosomes are carriers of potentially protective endogenous molecules, including microRNAs (miRNAs/miRs). The current study set out to test the effects of transferring miR-182-5p from MSC-derived exosomes into myocardial cells on myocardial I/R injury. First, an I/R mouse model was developed by left anterior descending coronary artery occlusion, and myocardial cells were exposed to hypoxia/reoxygenation (H/R) for in vitro I/R model establishment. Loss- and gain-of-function experiments of miR-182-5p and GSDMD were conducted to explore the effects of miR-182-5p via MSC-derived exosomes on cell pyroptosis and viability. GSDMD was robustly expressed in I/R-injured myocardial tissues and H/R-exposed myocardial cells. GSDMD upregulation promoted H/R-induced myocardial cell pyroptosis and reduced viability, corresponding to increased lactate dehydrogenase release, reactive oxygen species production, and pyroptosis. A luciferase assay demonstrated GSDMD as a target of miR-182-5p. In addition, exosomal miR-182-5p was found to diminish GSDMD-dependent cell pyroptosis and inflammation induced by H/R. Furthermore, MSC-derived exosomes carrying miR-182-5p improved cardiac function and reduced myocardial infarction, accompanied with reduced inflammation and cell pyroptosis in vivo. Taken together, our findings suggest a cardioprotective effect of exosomal miR-182-5p against myocardial I/R injury, shedding light on an attractive therapeutic strategy.https://doi.org/10.1038/s41420-022-00909-6 |
| spellingShingle | Rongchuan Yue Shengzhong Lu Yu Luo Jing Zeng Hao Liang Dan Qin Xiaobo Wang Tao Wang Jun Pu Houxiang Hu Mesenchymal stem cell-derived exosomal microRNA-182-5p alleviates myocardial ischemia/reperfusion injury by targeting GSDMD in mice Cell Death Discovery |
| title | Mesenchymal stem cell-derived exosomal microRNA-182-5p alleviates myocardial ischemia/reperfusion injury by targeting GSDMD in mice |
| title_full | Mesenchymal stem cell-derived exosomal microRNA-182-5p alleviates myocardial ischemia/reperfusion injury by targeting GSDMD in mice |
| title_fullStr | Mesenchymal stem cell-derived exosomal microRNA-182-5p alleviates myocardial ischemia/reperfusion injury by targeting GSDMD in mice |
| title_full_unstemmed | Mesenchymal stem cell-derived exosomal microRNA-182-5p alleviates myocardial ischemia/reperfusion injury by targeting GSDMD in mice |
| title_short | Mesenchymal stem cell-derived exosomal microRNA-182-5p alleviates myocardial ischemia/reperfusion injury by targeting GSDMD in mice |
| title_sort | mesenchymal stem cell derived exosomal microrna 182 5p alleviates myocardial ischemia reperfusion injury by targeting gsdmd in mice |
| url | https://doi.org/10.1038/s41420-022-00909-6 |
| work_keys_str_mv | AT rongchuanyue mesenchymalstemcellderivedexosomalmicrorna1825palleviatesmyocardialischemiareperfusioninjurybytargetinggsdmdinmice AT shengzhonglu mesenchymalstemcellderivedexosomalmicrorna1825palleviatesmyocardialischemiareperfusioninjurybytargetinggsdmdinmice AT yuluo mesenchymalstemcellderivedexosomalmicrorna1825palleviatesmyocardialischemiareperfusioninjurybytargetinggsdmdinmice AT jingzeng mesenchymalstemcellderivedexosomalmicrorna1825palleviatesmyocardialischemiareperfusioninjurybytargetinggsdmdinmice AT haoliang mesenchymalstemcellderivedexosomalmicrorna1825palleviatesmyocardialischemiareperfusioninjurybytargetinggsdmdinmice AT danqin mesenchymalstemcellderivedexosomalmicrorna1825palleviatesmyocardialischemiareperfusioninjurybytargetinggsdmdinmice AT xiaobowang mesenchymalstemcellderivedexosomalmicrorna1825palleviatesmyocardialischemiareperfusioninjurybytargetinggsdmdinmice AT taowang mesenchymalstemcellderivedexosomalmicrorna1825palleviatesmyocardialischemiareperfusioninjurybytargetinggsdmdinmice AT junpu mesenchymalstemcellderivedexosomalmicrorna1825palleviatesmyocardialischemiareperfusioninjurybytargetinggsdmdinmice AT houxianghu mesenchymalstemcellderivedexosomalmicrorna1825palleviatesmyocardialischemiareperfusioninjurybytargetinggsdmdinmice |