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Acid Sphingomyelinase Controls Early Phases of Skeletal Muscle Regeneration by Shaping the Macrophage Phenotype
Skeletal muscle regeneration is a complex process involving crosstalk between immune cells and myogenic precursor cells, i.e., satellite cells. In this scenario, macrophage recruitment in damaged muscles is a mandatory step for tissue repair since pro-inflammatory M1 macrophages promote the activati...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616363/ https://www.ncbi.nlm.nih.gov/pubmed/34831250 http://dx.doi.org/10.3390/cells10113028 |
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author | Roux-Biejat, Paulina Coazzoli, Marco Marrazzo, Pasquale Zecchini, Silvia Di Renzo, Ilaria Prata, Cecilia Napoli, Alessandra Moscheni, Claudia Giovarelli, Matteo Barbalace, Maria Cristina Catalani, Elisabetta Bassi, Maria Teresa De Palma, Clara Cervia, Davide Malaguti, Marco Hrelia, Silvana Clementi, Emilio Perrotta, Cristiana |
author_facet | Roux-Biejat, Paulina Coazzoli, Marco Marrazzo, Pasquale Zecchini, Silvia Di Renzo, Ilaria Prata, Cecilia Napoli, Alessandra Moscheni, Claudia Giovarelli, Matteo Barbalace, Maria Cristina Catalani, Elisabetta Bassi, Maria Teresa De Palma, Clara Cervia, Davide Malaguti, Marco Hrelia, Silvana Clementi, Emilio Perrotta, Cristiana |
author_sort | Roux-Biejat, Paulina |
collection | PubMed |
description | Skeletal muscle regeneration is a complex process involving crosstalk between immune cells and myogenic precursor cells, i.e., satellite cells. In this scenario, macrophage recruitment in damaged muscles is a mandatory step for tissue repair since pro-inflammatory M1 macrophages promote the activation of satellite cells, stimulating their proliferation and then, after switching into anti-inflammatory M2 macrophages, they prompt satellite cells’ differentiation into myotubes and resolve inflammation. Here, we show that acid sphingomyelinase (ASMase), a key enzyme in sphingolipid metabolism, is activated after skeletal muscle injury induced in vivo by the injection of cardiotoxin. ASMase ablation shortens the early phases of skeletal muscle regeneration without affecting satellite cell behavior. Of interest, ASMase regulates the balance between M1 and M2 macrophages in the injured muscles so that the absence of the enzyme reduces inflammation. The analysis of macrophage populations indicates that these events depend on the altered polarization of M1 macrophages towards an M2 phenotype. Our results unravel a novel role of ASMase in regulating immune response during muscle regeneration/repair and suggest ASMase as a supplemental therapeutic target in conditions of redundant inflammation that impairs muscle recovery. |
format | Online Article Text |
id | pubmed-8616363 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86163632021-11-26 Acid Sphingomyelinase Controls Early Phases of Skeletal Muscle Regeneration by Shaping the Macrophage Phenotype Roux-Biejat, Paulina Coazzoli, Marco Marrazzo, Pasquale Zecchini, Silvia Di Renzo, Ilaria Prata, Cecilia Napoli, Alessandra Moscheni, Claudia Giovarelli, Matteo Barbalace, Maria Cristina Catalani, Elisabetta Bassi, Maria Teresa De Palma, Clara Cervia, Davide Malaguti, Marco Hrelia, Silvana Clementi, Emilio Perrotta, Cristiana Cells Article Skeletal muscle regeneration is a complex process involving crosstalk between immune cells and myogenic precursor cells, i.e., satellite cells. In this scenario, macrophage recruitment in damaged muscles is a mandatory step for tissue repair since pro-inflammatory M1 macrophages promote the activation of satellite cells, stimulating their proliferation and then, after switching into anti-inflammatory M2 macrophages, they prompt satellite cells’ differentiation into myotubes and resolve inflammation. Here, we show that acid sphingomyelinase (ASMase), a key enzyme in sphingolipid metabolism, is activated after skeletal muscle injury induced in vivo by the injection of cardiotoxin. ASMase ablation shortens the early phases of skeletal muscle regeneration without affecting satellite cell behavior. Of interest, ASMase regulates the balance between M1 and M2 macrophages in the injured muscles so that the absence of the enzyme reduces inflammation. The analysis of macrophage populations indicates that these events depend on the altered polarization of M1 macrophages towards an M2 phenotype. Our results unravel a novel role of ASMase in regulating immune response during muscle regeneration/repair and suggest ASMase as a supplemental therapeutic target in conditions of redundant inflammation that impairs muscle recovery. MDPI 2021-11-05 /pmc/articles/PMC8616363/ /pubmed/34831250 http://dx.doi.org/10.3390/cells10113028 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Roux-Biejat, Paulina Coazzoli, Marco Marrazzo, Pasquale Zecchini, Silvia Di Renzo, Ilaria Prata, Cecilia Napoli, Alessandra Moscheni, Claudia Giovarelli, Matteo Barbalace, Maria Cristina Catalani, Elisabetta Bassi, Maria Teresa De Palma, Clara Cervia, Davide Malaguti, Marco Hrelia, Silvana Clementi, Emilio Perrotta, Cristiana Acid Sphingomyelinase Controls Early Phases of Skeletal Muscle Regeneration by Shaping the Macrophage Phenotype |
title | Acid Sphingomyelinase Controls Early Phases of Skeletal Muscle Regeneration by Shaping the Macrophage Phenotype |
title_full | Acid Sphingomyelinase Controls Early Phases of Skeletal Muscle Regeneration by Shaping the Macrophage Phenotype |
title_fullStr | Acid Sphingomyelinase Controls Early Phases of Skeletal Muscle Regeneration by Shaping the Macrophage Phenotype |
title_full_unstemmed | Acid Sphingomyelinase Controls Early Phases of Skeletal Muscle Regeneration by Shaping the Macrophage Phenotype |
title_short | Acid Sphingomyelinase Controls Early Phases of Skeletal Muscle Regeneration by Shaping the Macrophage Phenotype |
title_sort | acid sphingomyelinase controls early phases of skeletal muscle regeneration by shaping the macrophage phenotype |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616363/ https://www.ncbi.nlm.nih.gov/pubmed/34831250 http://dx.doi.org/10.3390/cells10113028 |
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