Loss of adenosine A3 receptors accelerates skeletal muscle regeneration in mice following cardiotoxin-induced injury
Abstract Skeletal muscle regeneration is a complex process orchestrated by multiple interacting steps. An increasing number of reports indicate that inflammatory responses play a central role in linking initial muscle injury responses to timely muscle regeneration following injury. The nucleoside ad...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-10-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-06228-7 |
| _version_ | 1797647196758212608 |
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| author | Nastaran Tarban Albert Bálint Papp Dávid Deák Péter Szentesi Hajnalka Halász Andreas Patsalos László Csernoch Zsolt Sarang Zsuzsa Szondy |
| author_facet | Nastaran Tarban Albert Bálint Papp Dávid Deák Péter Szentesi Hajnalka Halász Andreas Patsalos László Csernoch Zsolt Sarang Zsuzsa Szondy |
| author_sort | Nastaran Tarban |
| collection | DOAJ |
| description | Abstract Skeletal muscle regeneration is a complex process orchestrated by multiple interacting steps. An increasing number of reports indicate that inflammatory responses play a central role in linking initial muscle injury responses to timely muscle regeneration following injury. The nucleoside adenosine has been known for a long time as an endogenously produced anti-inflammatory molecule that is generated in high amounts during tissue injury. It mediates its physiological effects via four types of adenosine receptors. From these, adenosine A3 receptors (A3Rs) are not expressed by the skeletal muscle but are present on the surface of various inflammatory cells. In the present paper, the effect of the loss of A3Rs was investigated on the regeneration of the tibialis anterior (TA) muscle in mice following cardiotoxin-induced injury. Here we report that regeneration of the skeletal muscle from A3R−/− mice is characterized by a stronger initial inflammatory response resulting in a larger number of transmigrating inflammatory cells to the injury site, faster clearance of cell debris, enhanced proliferation and faster differentiation of the satellite cells (the muscle stem cells), and increased fusion of the generated myoblasts. This leads to accelerated skeletal muscle tissue repair and the formation of larger myofibers. Though the infiltrating immune cells expressed A3Rs and showed an increased inflammatory profile in the injured A3R−/− muscles, bone marrow transplantation experiments revealed that the increased response of the tissue-resident cells to tissue injury is responsible for the observed phenomenon. Altogether our data indicate that A3Rs are negative regulators of injury-related regenerative inflammation and consequently also that of the muscle fiber growth in the TA muscle. Thus, inhibiting A3Rs might have a therapeutic value during skeletal muscle regeneration following injury. |
| first_indexed | 2024-03-11T15:12:47Z |
| format | Article |
| id | doaj.art-720810c6a7ae4f4a94e8a4ef1ab9f47f |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-03-11T15:12:47Z |
| publishDate | 2023-10-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-720810c6a7ae4f4a94e8a4ef1ab9f47f2023-10-29T12:37:56ZengNature Publishing GroupCell Death and Disease2041-48892023-10-01141011310.1038/s41419-023-06228-7Loss of adenosine A3 receptors accelerates skeletal muscle regeneration in mice following cardiotoxin-induced injuryNastaran Tarban0Albert Bálint Papp1Dávid Deák2Péter Szentesi3Hajnalka Halász4Andreas Patsalos5László Csernoch6Zsolt Sarang7Zsuzsa Szondy8Doctoral School of Molecular Cell and Immune Biology, University of DebrecenDoctoral School of Dental Sciences, University of DebrecenLaboratory Animal Facility, Life Science Building, University of DebrecenDepartment of Physiology, Faculty of Medicine, University of DebrecenDoctoral School of Molecular Cell and Immune Biology, University of DebrecenDepartments of Medicine and Biological Chemistry, Johns Hopkins University School of Medicine, Institute for Fundamental Biomedical Research, Johns Hopkins All Children’s Hospital, StDepartment of Physiology, Faculty of Medicine, University of DebrecenDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, University of DebrecenDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, University of DebrecenAbstract Skeletal muscle regeneration is a complex process orchestrated by multiple interacting steps. An increasing number of reports indicate that inflammatory responses play a central role in linking initial muscle injury responses to timely muscle regeneration following injury. The nucleoside adenosine has been known for a long time as an endogenously produced anti-inflammatory molecule that is generated in high amounts during tissue injury. It mediates its physiological effects via four types of adenosine receptors. From these, adenosine A3 receptors (A3Rs) are not expressed by the skeletal muscle but are present on the surface of various inflammatory cells. In the present paper, the effect of the loss of A3Rs was investigated on the regeneration of the tibialis anterior (TA) muscle in mice following cardiotoxin-induced injury. Here we report that regeneration of the skeletal muscle from A3R−/− mice is characterized by a stronger initial inflammatory response resulting in a larger number of transmigrating inflammatory cells to the injury site, faster clearance of cell debris, enhanced proliferation and faster differentiation of the satellite cells (the muscle stem cells), and increased fusion of the generated myoblasts. This leads to accelerated skeletal muscle tissue repair and the formation of larger myofibers. Though the infiltrating immune cells expressed A3Rs and showed an increased inflammatory profile in the injured A3R−/− muscles, bone marrow transplantation experiments revealed that the increased response of the tissue-resident cells to tissue injury is responsible for the observed phenomenon. Altogether our data indicate that A3Rs are negative regulators of injury-related regenerative inflammation and consequently also that of the muscle fiber growth in the TA muscle. Thus, inhibiting A3Rs might have a therapeutic value during skeletal muscle regeneration following injury.https://doi.org/10.1038/s41419-023-06228-7 |
| spellingShingle | Nastaran Tarban Albert Bálint Papp Dávid Deák Péter Szentesi Hajnalka Halász Andreas Patsalos László Csernoch Zsolt Sarang Zsuzsa Szondy Loss of adenosine A3 receptors accelerates skeletal muscle regeneration in mice following cardiotoxin-induced injury Cell Death and Disease |
| title | Loss of adenosine A3 receptors accelerates skeletal muscle regeneration in mice following cardiotoxin-induced injury |
| title_full | Loss of adenosine A3 receptors accelerates skeletal muscle regeneration in mice following cardiotoxin-induced injury |
| title_fullStr | Loss of adenosine A3 receptors accelerates skeletal muscle regeneration in mice following cardiotoxin-induced injury |
| title_full_unstemmed | Loss of adenosine A3 receptors accelerates skeletal muscle regeneration in mice following cardiotoxin-induced injury |
| title_short | Loss of adenosine A3 receptors accelerates skeletal muscle regeneration in mice following cardiotoxin-induced injury |
| title_sort | loss of adenosine a3 receptors accelerates skeletal muscle regeneration in mice following cardiotoxin induced injury |
| url | https://doi.org/10.1038/s41419-023-06228-7 |
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