Regenerating Skeletal Muscle Compensates for the Impaired Macrophage Functions Leading to Normal Muscle Repair in Retinol Saturase Null Mice
Skeletal muscle repair is initiated by local inflammation and involves the engulfment of dead cells (efferocytosis) by infiltrating macrophages at the injury site. Macrophages orchestrate the whole repair program, and efferocytosis is a key event not only for cell clearance but also for triggering t...
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MDPI AG
2022-04-01
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| author | Nastaran Tarban Hajnalka Halász Péter Gogolák Éva Garabuczi Alexander R. Moise Krzysztof Palczewski Zsolt Sarang Zsuzsa Szondy |
| author_facet | Nastaran Tarban Hajnalka Halász Péter Gogolák Éva Garabuczi Alexander R. Moise Krzysztof Palczewski Zsolt Sarang Zsuzsa Szondy |
| author_sort | Nastaran Tarban |
| collection | DOAJ |
| description | Skeletal muscle repair is initiated by local inflammation and involves the engulfment of dead cells (efferocytosis) by infiltrating macrophages at the injury site. Macrophages orchestrate the whole repair program, and efferocytosis is a key event not only for cell clearance but also for triggering the timed polarization of the inflammatory phenotype of macrophages into the healing one. While pro-inflammatory cytokines produced by the inflammatory macrophages induce satellite cell proliferation and differentiation into myoblasts, healing macrophages initiate the resolution of inflammation, angiogenesis, and extracellular matrix formation and drive myoblast fusion and myotube growth. Therefore, improper efferocytosis results in impaired muscle repair. Retinol saturase (RetSat) initiates the formation of various dihydroretinoids, a group of vitamin A derivatives that regulate transcription by activating retinoid receptors. Previous studies from our laboratory have shown that RetSat-null macrophages produce less milk fat globule-epidermal growth factor-factor-8 (MFG-E8), lack neuropeptide Y expression, and are characterized by impaired efferocytosis. Here, we investigated skeletal muscle repair in the tibialis anterior muscle of RetSat-null mice following cardiotoxin injury. Our data presented here demonstrate that, unexpectedly, several cell types participating in skeletal muscle regeneration compensate for the impaired macrophage functions, resulting in normal muscle repair in the RetSat-null mice. |
| first_indexed | 2024-03-09T11:01:22Z |
| format | Article |
| id | doaj.art-98625e4602194198bf82f23f14b23a7f |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T11:01:22Z |
| publishDate | 2022-04-01 |
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| record_format | Article |
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| spelling | doaj.art-98625e4602194198bf82f23f14b23a7f2023-12-01T01:14:39ZengMDPI AGCells2073-44092022-04-01118133310.3390/cells11081333Regenerating Skeletal Muscle Compensates for the Impaired Macrophage Functions Leading to Normal Muscle Repair in Retinol Saturase Null MiceNastaran Tarban0Hajnalka Halász1Péter Gogolák2Éva Garabuczi3Alexander R. Moise4Krzysztof Palczewski5Zsolt Sarang6Zsuzsa Szondy7Doctoral School of Molecular Cell and Immune Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryDoctoral School of Molecular Cell and Immune Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryDepartment of Immunology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryMedical Sciences Division, Northern Ontario School of Medicine, Sudbury, ON P3E 2C6, CanadaDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA 92697, USADepartment of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungaryDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, HungarySkeletal muscle repair is initiated by local inflammation and involves the engulfment of dead cells (efferocytosis) by infiltrating macrophages at the injury site. Macrophages orchestrate the whole repair program, and efferocytosis is a key event not only for cell clearance but also for triggering the timed polarization of the inflammatory phenotype of macrophages into the healing one. While pro-inflammatory cytokines produced by the inflammatory macrophages induce satellite cell proliferation and differentiation into myoblasts, healing macrophages initiate the resolution of inflammation, angiogenesis, and extracellular matrix formation and drive myoblast fusion and myotube growth. Therefore, improper efferocytosis results in impaired muscle repair. Retinol saturase (RetSat) initiates the formation of various dihydroretinoids, a group of vitamin A derivatives that regulate transcription by activating retinoid receptors. Previous studies from our laboratory have shown that RetSat-null macrophages produce less milk fat globule-epidermal growth factor-factor-8 (MFG-E8), lack neuropeptide Y expression, and are characterized by impaired efferocytosis. Here, we investigated skeletal muscle repair in the tibialis anterior muscle of RetSat-null mice following cardiotoxin injury. Our data presented here demonstrate that, unexpectedly, several cell types participating in skeletal muscle regeneration compensate for the impaired macrophage functions, resulting in normal muscle repair in the RetSat-null mice.https://www.mdpi.com/2073-4409/11/8/1333cardiotoxin injuryretinol saturaseneuropeptide YMFG-E8efferocytosisskeletal muscle repair |
| spellingShingle | Nastaran Tarban Hajnalka Halász Péter Gogolák Éva Garabuczi Alexander R. Moise Krzysztof Palczewski Zsolt Sarang Zsuzsa Szondy Regenerating Skeletal Muscle Compensates for the Impaired Macrophage Functions Leading to Normal Muscle Repair in Retinol Saturase Null Mice Cells cardiotoxin injury retinol saturase neuropeptide Y MFG-E8 efferocytosis skeletal muscle repair |
| title | Regenerating Skeletal Muscle Compensates for the Impaired Macrophage Functions Leading to Normal Muscle Repair in Retinol Saturase Null Mice |
| title_full | Regenerating Skeletal Muscle Compensates for the Impaired Macrophage Functions Leading to Normal Muscle Repair in Retinol Saturase Null Mice |
| title_fullStr | Regenerating Skeletal Muscle Compensates for the Impaired Macrophage Functions Leading to Normal Muscle Repair in Retinol Saturase Null Mice |
| title_full_unstemmed | Regenerating Skeletal Muscle Compensates for the Impaired Macrophage Functions Leading to Normal Muscle Repair in Retinol Saturase Null Mice |
| title_short | Regenerating Skeletal Muscle Compensates for the Impaired Macrophage Functions Leading to Normal Muscle Repair in Retinol Saturase Null Mice |
| title_sort | regenerating skeletal muscle compensates for the impaired macrophage functions leading to normal muscle repair in retinol saturase null mice |
| topic | cardiotoxin injury retinol saturase neuropeptide Y MFG-E8 efferocytosis skeletal muscle repair |
| url | https://www.mdpi.com/2073-4409/11/8/1333 |
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