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The super-healing MRL strain promotes muscle growth in muscular dystrophy through a regenerative extracellular matrix
Genetic background shifts the severity of muscular dystrophy. In mice, the DBA/2J strain confers a more severe muscular dystrophy phenotype, whereas the Murphy’s Roth Large (MRL) strain has “super-healing” properties that reduce fibrosis. A comparative analysis of the Sgcg null model of Limb Girdle...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10327155/ https://www.ncbi.nlm.nih.gov/pubmed/37425960 http://dx.doi.org/10.1101/2023.06.29.547098 |
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author | O’Brien, Joseph G. Willis, Alexander B. Long, Ashlee M. Kwon, Jason Lee, GaHyun Li, Frank Page, Patrick G.T. Vo, Andy H. Hadhazy, Michele Crosbie, Rachelle H. Demonbreun, Alexis R. McNally, Elizabeth M. |
author_facet | O’Brien, Joseph G. Willis, Alexander B. Long, Ashlee M. Kwon, Jason Lee, GaHyun Li, Frank Page, Patrick G.T. Vo, Andy H. Hadhazy, Michele Crosbie, Rachelle H. Demonbreun, Alexis R. McNally, Elizabeth M. |
author_sort | O’Brien, Joseph G. |
collection | PubMed |
description | Genetic background shifts the severity of muscular dystrophy. In mice, the DBA/2J strain confers a more severe muscular dystrophy phenotype, whereas the Murphy’s Roth Large (MRL) strain has “super-healing” properties that reduce fibrosis. A comparative analysis of the Sgcg null model of Limb Girdle Muscular Dystrophy in the DBA/2J versus MRL strain showed the MRL background was associated with greater myofiber regeneration and reduced structural degradation of muscle. Transcriptomic profiling of dystrophic muscle in the DBA/2J and MRL strains indicated strain-dependent expression of the extracellular matrix (ECM) and TGF-β signaling genes. To investigate the MRL ECM, cellular components were removed from dystrophic muscle sections to generate decellularized “myoscaffolds”. Decellularized myoscaffolds from dystrophic mice in the protective MRL strain had significantly less deposition of collagen and matrix-bound TGF-β1 and TGF-β3 throughout the matrix, and dystrophic myoscaffolds from the MRL background were enriched in myokines. C2C12 myoblasts were seeded onto decellularized matrices from Sgcg(−/−) MRL and Sgcg(−/−) DBA/2J matrices. Acellular myoscaffolds from the dystrophic MRL background induced myoblast differentiation and growth compared to dystrophic myoscaffolds from the DBA/2J matrices. These studies establish that the MRL background also generates its effect through a highly regenerative ECM, which is active even in muscular dystrophy. |
format | Online Article Text |
id | pubmed-10327155 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-103271552023-07-08 The super-healing MRL strain promotes muscle growth in muscular dystrophy through a regenerative extracellular matrix O’Brien, Joseph G. Willis, Alexander B. Long, Ashlee M. Kwon, Jason Lee, GaHyun Li, Frank Page, Patrick G.T. Vo, Andy H. Hadhazy, Michele Crosbie, Rachelle H. Demonbreun, Alexis R. McNally, Elizabeth M. bioRxiv Article Genetic background shifts the severity of muscular dystrophy. In mice, the DBA/2J strain confers a more severe muscular dystrophy phenotype, whereas the Murphy’s Roth Large (MRL) strain has “super-healing” properties that reduce fibrosis. A comparative analysis of the Sgcg null model of Limb Girdle Muscular Dystrophy in the DBA/2J versus MRL strain showed the MRL background was associated with greater myofiber regeneration and reduced structural degradation of muscle. Transcriptomic profiling of dystrophic muscle in the DBA/2J and MRL strains indicated strain-dependent expression of the extracellular matrix (ECM) and TGF-β signaling genes. To investigate the MRL ECM, cellular components were removed from dystrophic muscle sections to generate decellularized “myoscaffolds”. Decellularized myoscaffolds from dystrophic mice in the protective MRL strain had significantly less deposition of collagen and matrix-bound TGF-β1 and TGF-β3 throughout the matrix, and dystrophic myoscaffolds from the MRL background were enriched in myokines. C2C12 myoblasts were seeded onto decellularized matrices from Sgcg(−/−) MRL and Sgcg(−/−) DBA/2J matrices. Acellular myoscaffolds from the dystrophic MRL background induced myoblast differentiation and growth compared to dystrophic myoscaffolds from the DBA/2J matrices. These studies establish that the MRL background also generates its effect through a highly regenerative ECM, which is active even in muscular dystrophy. Cold Spring Harbor Laboratory 2023-06-30 /pmc/articles/PMC10327155/ /pubmed/37425960 http://dx.doi.org/10.1101/2023.06.29.547098 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article O’Brien, Joseph G. Willis, Alexander B. Long, Ashlee M. Kwon, Jason Lee, GaHyun Li, Frank Page, Patrick G.T. Vo, Andy H. Hadhazy, Michele Crosbie, Rachelle H. Demonbreun, Alexis R. McNally, Elizabeth M. The super-healing MRL strain promotes muscle growth in muscular dystrophy through a regenerative extracellular matrix |
title | The super-healing MRL strain promotes muscle growth in muscular dystrophy through a regenerative extracellular matrix |
title_full | The super-healing MRL strain promotes muscle growth in muscular dystrophy through a regenerative extracellular matrix |
title_fullStr | The super-healing MRL strain promotes muscle growth in muscular dystrophy through a regenerative extracellular matrix |
title_full_unstemmed | The super-healing MRL strain promotes muscle growth in muscular dystrophy through a regenerative extracellular matrix |
title_short | The super-healing MRL strain promotes muscle growth in muscular dystrophy through a regenerative extracellular matrix |
title_sort | super-healing mrl strain promotes muscle growth in muscular dystrophy through a regenerative extracellular matrix |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10327155/ https://www.ncbi.nlm.nih.gov/pubmed/37425960 http://dx.doi.org/10.1101/2023.06.29.547098 |
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