Cargando…
Mesenchymal stem cell-derived exosomal microRNA-182-5p alleviates myocardial ischemia/reperfusion injury by targeting GSDMD in mice
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 tes...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9010441/ https://www.ncbi.nlm.nih.gov/pubmed/35422485 http://dx.doi.org/10.1038/s41420-022-00909-6 |
_version_ | 1784687477205762048 |
---|---|
author | Yue, Rongchuan Lu, Shengzhong Luo, Yu Zeng, Jing Liang, Hao Qin, Dan Wang, Xiaobo Wang, Tao Pu, Jun Hu, Houxiang |
author_facet | Yue, Rongchuan Lu, Shengzhong Luo, Yu Zeng, Jing Liang, Hao Qin, Dan Wang, Xiaobo Wang, Tao Pu, Jun Hu, Houxiang |
author_sort | Yue, Rongchuan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9010441 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-90104412022-04-28 Mesenchymal stem cell-derived exosomal microRNA-182-5p alleviates myocardial ischemia/reperfusion injury by targeting GSDMD in mice Yue, Rongchuan Lu, Shengzhong Luo, Yu Zeng, Jing Liang, Hao Qin, Dan Wang, Xiaobo Wang, Tao Pu, Jun Hu, Houxiang Cell Death Discov Article 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. Nature Publishing Group UK 2022-04-14 /pmc/articles/PMC9010441/ /pubmed/35422485 http://dx.doi.org/10.1038/s41420-022-00909-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Yue, Rongchuan Lu, Shengzhong Luo, Yu Zeng, Jing Liang, Hao Qin, Dan Wang, Xiaobo Wang, Tao Pu, Jun Hu, Houxiang Mesenchymal stem cell-derived exosomal microRNA-182-5p alleviates myocardial ischemia/reperfusion injury by targeting GSDMD in mice |
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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9010441/ https://www.ncbi.nlm.nih.gov/pubmed/35422485 http://dx.doi.org/10.1038/s41420-022-00909-6 |
work_keys_str_mv | AT yuerongchuan mesenchymalstemcellderivedexosomalmicrorna1825palleviatesmyocardialischemiareperfusioninjurybytargetinggsdmdinmice AT lushengzhong mesenchymalstemcellderivedexosomalmicrorna1825palleviatesmyocardialischemiareperfusioninjurybytargetinggsdmdinmice AT luoyu mesenchymalstemcellderivedexosomalmicrorna1825palleviatesmyocardialischemiareperfusioninjurybytargetinggsdmdinmice AT zengjing mesenchymalstemcellderivedexosomalmicrorna1825palleviatesmyocardialischemiareperfusioninjurybytargetinggsdmdinmice AT lianghao mesenchymalstemcellderivedexosomalmicrorna1825palleviatesmyocardialischemiareperfusioninjurybytargetinggsdmdinmice AT qindan mesenchymalstemcellderivedexosomalmicrorna1825palleviatesmyocardialischemiareperfusioninjurybytargetinggsdmdinmice AT wangxiaobo mesenchymalstemcellderivedexosomalmicrorna1825palleviatesmyocardialischemiareperfusioninjurybytargetinggsdmdinmice AT wangtao mesenchymalstemcellderivedexosomalmicrorna1825palleviatesmyocardialischemiareperfusioninjurybytargetinggsdmdinmice AT pujun mesenchymalstemcellderivedexosomalmicrorna1825palleviatesmyocardialischemiareperfusioninjurybytargetinggsdmdinmice AT huhouxiang mesenchymalstemcellderivedexosomalmicrorna1825palleviatesmyocardialischemiareperfusioninjurybytargetinggsdmdinmice |