Y RNA fragment in extracellular vesicles confers cardioprotection via modulation of IL‐10 expression and secretion
Abstract Cardiosphere‐derived cells (CDCs) reduce myocardial infarct size via secreted extracellular vesicles (CDC‐EVs), including exosomes, which alter macrophage polarization. We questioned whether short non‐coding RNA species of unknown function within CDC‐EVs contribute to cardioprotection. The...
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| Format: | Article |
| Language: | English |
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Springer Nature
2017-02-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.201606924 |
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| author | Linda Cambier Geoffrey de Couto Ahmed Ibrahim Antonio K Echavez Jackelyn Valle Weixin Liu Michelle Kreke Rachel R Smith Linda Marbán Eduardo Marbán |
| author_facet | Linda Cambier Geoffrey de Couto Ahmed Ibrahim Antonio K Echavez Jackelyn Valle Weixin Liu Michelle Kreke Rachel R Smith Linda Marbán Eduardo Marbán |
| author_sort | Linda Cambier |
| collection | DOAJ |
| description | Abstract Cardiosphere‐derived cells (CDCs) reduce myocardial infarct size via secreted extracellular vesicles (CDC‐EVs), including exosomes, which alter macrophage polarization. We questioned whether short non‐coding RNA species of unknown function within CDC‐EVs contribute to cardioprotection. The most abundant RNA species in CDC‐EVs is a Y RNA fragment (EV‐YF1); its relative abundance in CDC‐EVs correlates with CDC potency in vivo. Fluorescently labeled EV‐YF1 is actively transferred from CDCs to target macrophages via CDC‐EVs. Direct transfection of macrophages with EV‐YF1 induced transcription and secretion of IL‐10. When cocultured with rat cardiomyocytes, EV‐YF1‐primed macrophages were potently cytoprotective toward oxidatively stressed cardiomyocytes through induction of IL‐10. In vivo, intracoronary injection of EV‐YF1 following ischemia/reperfusion reduced infarct size. A fragment of Y RNA, highly enriched in CDC‐EVs, alters Il10 gene expression and enhances IL‐10 protein secretion. The demonstration that EV‐YF1 confers cardioprotection highlights the potential importance of diverse exosomal contents of unknown function, above and beyond the usual suspects (e.g., microRNAs and proteins). |
| format | Article |
| id | doaj-art-1565724645d04bdea2518be0a581c8fb |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2017-02-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-1565724645d04bdea2518be0a581c8fb2025-08-20T03:43:29ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842017-02-019333735210.15252/emmm.201606924Y RNA fragment in extracellular vesicles confers cardioprotection via modulation of IL‐10 expression and secretionLinda Cambier0Geoffrey de Couto1Ahmed Ibrahim2Antonio K Echavez3Jackelyn Valle4Weixin Liu5Michelle Kreke6Rachel R Smith7Linda Marbán8Eduardo Marbán9Cedars‐Sinai Heart Institute, Cedars‐Sinai Medical CenterCedars‐Sinai Heart Institute, Cedars‐Sinai Medical CenterCapricor Inc.Cedars‐Sinai Heart Institute, Cedars‐Sinai Medical CenterCedars‐Sinai Heart Institute, Cedars‐Sinai Medical CenterCedars‐Sinai Heart Institute, Cedars‐Sinai Medical CenterCapricor Inc.Capricor Inc.Capricor Inc.Cedars‐Sinai Heart Institute, Cedars‐Sinai Medical CenterAbstract Cardiosphere‐derived cells (CDCs) reduce myocardial infarct size via secreted extracellular vesicles (CDC‐EVs), including exosomes, which alter macrophage polarization. We questioned whether short non‐coding RNA species of unknown function within CDC‐EVs contribute to cardioprotection. The most abundant RNA species in CDC‐EVs is a Y RNA fragment (EV‐YF1); its relative abundance in CDC‐EVs correlates with CDC potency in vivo. Fluorescently labeled EV‐YF1 is actively transferred from CDCs to target macrophages via CDC‐EVs. Direct transfection of macrophages with EV‐YF1 induced transcription and secretion of IL‐10. When cocultured with rat cardiomyocytes, EV‐YF1‐primed macrophages were potently cytoprotective toward oxidatively stressed cardiomyocytes through induction of IL‐10. In vivo, intracoronary injection of EV‐YF1 following ischemia/reperfusion reduced infarct size. A fragment of Y RNA, highly enriched in CDC‐EVs, alters Il10 gene expression and enhances IL‐10 protein secretion. The demonstration that EV‐YF1 confers cardioprotection highlights the potential importance of diverse exosomal contents of unknown function, above and beyond the usual suspects (e.g., microRNAs and proteins).https://doi.org/10.15252/emmm.201606924extracellular vesiclemacrophageRNAstem cells |
| spellingShingle | Linda Cambier Geoffrey de Couto Ahmed Ibrahim Antonio K Echavez Jackelyn Valle Weixin Liu Michelle Kreke Rachel R Smith Linda Marbán Eduardo Marbán Y RNA fragment in extracellular vesicles confers cardioprotection via modulation of IL‐10 expression and secretion EMBO Molecular Medicine extracellular vesicle macrophage RNA stem cells |
| title | Y RNA fragment in extracellular vesicles confers cardioprotection via modulation of IL‐10 expression and secretion |
| title_full | Y RNA fragment in extracellular vesicles confers cardioprotection via modulation of IL‐10 expression and secretion |
| title_fullStr | Y RNA fragment in extracellular vesicles confers cardioprotection via modulation of IL‐10 expression and secretion |
| title_full_unstemmed | Y RNA fragment in extracellular vesicles confers cardioprotection via modulation of IL‐10 expression and secretion |
| title_short | Y RNA fragment in extracellular vesicles confers cardioprotection via modulation of IL‐10 expression and secretion |
| title_sort | y rna fragment in extracellular vesicles confers cardioprotection via modulation of il 10 expression and secretion |
| topic | extracellular vesicle macrophage RNA stem cells |
| url | https://doi.org/10.15252/emmm.201606924 |
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