Cyclic Hypoxia Conditioning Alters the Content of Myoblast-Derived Extracellular Vesicles and Enhances Their Cell-Protective Functions
Remote ischemic conditioning (RIC) is a procedure that can attenuate ischemic-reperfusion injury by conducting brief cycles of ischemia and reperfusion in the arm or leg. Extracellular vesicles (EVs) circulating in the bloodstream can release their content into recipient cells to confer protective f...
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MDPI AG
2021-09-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/9/1211 |
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| author | Yan Yan Tingting Gu Stine Duelund Kaas Christensen Junyi Su Thomas Ravn Lassen Marie Vognstoft Hjortbak IJu Lo Susanne Trillingsgaard Venø Andrea Erzsebet Tóth Ping Song Morten Schallburg Nielsen Hans Erik Bøtker Blagoy Blagoev Kim Ryun Drasbek Jørgen Kjems |
| author_facet | Yan Yan Tingting Gu Stine Duelund Kaas Christensen Junyi Su Thomas Ravn Lassen Marie Vognstoft Hjortbak IJu Lo Susanne Trillingsgaard Venø Andrea Erzsebet Tóth Ping Song Morten Schallburg Nielsen Hans Erik Bøtker Blagoy Blagoev Kim Ryun Drasbek Jørgen Kjems |
| author_sort | Yan Yan |
| collection | DOAJ |
| description | Remote ischemic conditioning (RIC) is a procedure that can attenuate ischemic-reperfusion injury by conducting brief cycles of ischemia and reperfusion in the arm or leg. Extracellular vesicles (EVs) circulating in the bloodstream can release their content into recipient cells to confer protective function on ischemia-reperfusion injured (IRI) organs. Skeletal muscle cells are potential candidates to release EVs as a protective signal during RIC. In this study, we used C2C12 cells as a model system and performed cyclic hypoxia-reoxygenation (HR) to mimic RIC. EVs were collected and subjected to small RNA profiling and proteomics. HR induced a distinct shift in the miRNA profile and protein content in EVs. HR EV treatment restored cell viability, dampened inflammation, and enhanced tube formation in in vitro assays. In vivo, HR EVs showed increased accumulation in the ischemic brain compared to EVs secreted from normoxic culture (N EVs) in a mouse undergoing transient middle cerebral artery occlusion (tMCAO). We conclude that HR conditioning changes the miRNA and protein profile in EVs released by C2C12 cells and enhances the protective signal in the EVs to recipient cells in vitro. |
| first_indexed | 2024-03-10T07:51:53Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T07:51:53Z |
| publishDate | 2021-09-01 |
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| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-0d5ce58e6c3843c0924eb43e1462c7162023-11-22T12:08:41ZengMDPI AGBiomedicines2227-90592021-09-0199121110.3390/biomedicines9091211Cyclic Hypoxia Conditioning Alters the Content of Myoblast-Derived Extracellular Vesicles and Enhances Their Cell-Protective FunctionsYan Yan0Tingting Gu1Stine Duelund Kaas Christensen2Junyi Su3Thomas Ravn Lassen4Marie Vognstoft Hjortbak5IJu Lo6Susanne Trillingsgaard Venø7Andrea Erzsebet Tóth8Ping Song9Morten Schallburg Nielsen10Hans Erik Bøtker11Blagoy Blagoev12Kim Ryun Drasbek13Jørgen Kjems14Interdisciplinary Nanoscience Center, Aarhus University, 8000 Aarhus, DenmarkCenter of Functionally Integrative Neuroscience, Department of Clinical Medicine, Aarhus University, 8000 Aarhus, DenmarkDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense, DenmarkInterdisciplinary Nanoscience Center, Aarhus University, 8000 Aarhus, DenmarkDepartment of Cardiology, Aarhus University Hospital, Skejby, 8200 Aarhus, DenmarkDepartment of Cardiology, Aarhus University Hospital, Skejby, 8200 Aarhus, DenmarkInterdisciplinary Nanoscience Center, Aarhus University, 8000 Aarhus, DenmarkOmiics ApS, 8200 Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, 8000 Aarhus, DenmarkInterdisciplinary Nanoscience Center, Aarhus University, 8000 Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, 8000 Aarhus, DenmarkDepartment of Cardiology, Aarhus University Hospital, Skejby, 8200 Aarhus, DenmarkDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense, DenmarkCenter of Functionally Integrative Neuroscience, Department of Clinical Medicine, Aarhus University, 8000 Aarhus, DenmarkInterdisciplinary Nanoscience Center, Aarhus University, 8000 Aarhus, DenmarkRemote ischemic conditioning (RIC) is a procedure that can attenuate ischemic-reperfusion injury by conducting brief cycles of ischemia and reperfusion in the arm or leg. Extracellular vesicles (EVs) circulating in the bloodstream can release their content into recipient cells to confer protective function on ischemia-reperfusion injured (IRI) organs. Skeletal muscle cells are potential candidates to release EVs as a protective signal during RIC. In this study, we used C2C12 cells as a model system and performed cyclic hypoxia-reoxygenation (HR) to mimic RIC. EVs were collected and subjected to small RNA profiling and proteomics. HR induced a distinct shift in the miRNA profile and protein content in EVs. HR EV treatment restored cell viability, dampened inflammation, and enhanced tube formation in in vitro assays. In vivo, HR EVs showed increased accumulation in the ischemic brain compared to EVs secreted from normoxic culture (N EVs) in a mouse undergoing transient middle cerebral artery occlusion (tMCAO). We conclude that HR conditioning changes the miRNA and protein profile in EVs released by C2C12 cells and enhances the protective signal in the EVs to recipient cells in vitro.https://www.mdpi.com/2227-9059/9/9/1211remote ischemic conditioningmyoblastcyclic hypoxia-reoxygenationextracellular vesiclesmicroRNAsproteins |
| spellingShingle | Yan Yan Tingting Gu Stine Duelund Kaas Christensen Junyi Su Thomas Ravn Lassen Marie Vognstoft Hjortbak IJu Lo Susanne Trillingsgaard Venø Andrea Erzsebet Tóth Ping Song Morten Schallburg Nielsen Hans Erik Bøtker Blagoy Blagoev Kim Ryun Drasbek Jørgen Kjems Cyclic Hypoxia Conditioning Alters the Content of Myoblast-Derived Extracellular Vesicles and Enhances Their Cell-Protective Functions Biomedicines remote ischemic conditioning myoblast cyclic hypoxia-reoxygenation extracellular vesicles microRNAs proteins |
| title | Cyclic Hypoxia Conditioning Alters the Content of Myoblast-Derived Extracellular Vesicles and Enhances Their Cell-Protective Functions |
| title_full | Cyclic Hypoxia Conditioning Alters the Content of Myoblast-Derived Extracellular Vesicles and Enhances Their Cell-Protective Functions |
| title_fullStr | Cyclic Hypoxia Conditioning Alters the Content of Myoblast-Derived Extracellular Vesicles and Enhances Their Cell-Protective Functions |
| title_full_unstemmed | Cyclic Hypoxia Conditioning Alters the Content of Myoblast-Derived Extracellular Vesicles and Enhances Their Cell-Protective Functions |
| title_short | Cyclic Hypoxia Conditioning Alters the Content of Myoblast-Derived Extracellular Vesicles and Enhances Their Cell-Protective Functions |
| title_sort | cyclic hypoxia conditioning alters the content of myoblast derived extracellular vesicles and enhances their cell protective functions |
| topic | remote ischemic conditioning myoblast cyclic hypoxia-reoxygenation extracellular vesicles microRNAs proteins |
| url | https://www.mdpi.com/2227-9059/9/9/1211 |
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