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Up-regulation of Toll-like receptors 7 and 9 and its potential implications in the pathogenic mechanisms of LMNA-related myopathies

Laminopathies are a heterogeneous group of diseases, caused by mutations in lamin A/C proteins. The most common laminopathy (LMNA-related myopathies, LMNA-RM) affects skeletal and cardiac muscles; muscle histopathology is variable, ranging from mild unspecific changes to dystrophic features, sometim...

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Autores principales: Cappelletti, Cristina, Salerno, Franco, Canioni, Eleonora, Mora, Marina, Mantegazza, Renato, Bernasconi, Pia, Maggi, Lorenzo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000140/
https://www.ncbi.nlm.nih.gov/pubmed/29895224
http://dx.doi.org/10.1080/19491034.2018.1471947
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author Cappelletti, Cristina
Salerno, Franco
Canioni, Eleonora
Mora, Marina
Mantegazza, Renato
Bernasconi, Pia
Maggi, Lorenzo
author_facet Cappelletti, Cristina
Salerno, Franco
Canioni, Eleonora
Mora, Marina
Mantegazza, Renato
Bernasconi, Pia
Maggi, Lorenzo
author_sort Cappelletti, Cristina
collection PubMed
description Laminopathies are a heterogeneous group of diseases, caused by mutations in lamin A/C proteins. The most common laminopathy (LMNA-related myopathies, LMNA-RM) affects skeletal and cardiac muscles; muscle histopathology is variable, ranging from mild unspecific changes to dystrophic features, sometimes with inflammatory evidence. Whether the genetic defect might activate innate immune components, leading to chronic inflammation, myofiber necrosis and fibrosis, is still unknown. By qPCR, a significant up-regulation of Toll-like receptor (TLR) 7 and 9 transcripts was found in LMNA-RM compared to other myopathic and non-myopathic muscles. A marked TLR7/9 staining was observed on LMNA-RM blood vessels and muscle fibers and, when present, on infiltrating cells, mainly macrophages, scattered in the tissue or localized close to degenerated muscle fibers and connective tissue. Our results recognize innate immunity as a player in LMNA-RM pathogenesis. Modulation of TLR7/9 signaling pathways and decrease of macrophage-mediated inflammation might be potential therapeutic strategies in LMNA-RM management. Abbreviations: DMD, Duchenne muscular dystrophy; EDMD2, Emery-Dreifuss muscular dystrophy type 2; FSHD, facio-scapulo-humeral muscular dystrophy; LGMD1B, limb-girdle muscular dystrophy type 1B; LMNA-CMD, LMNA-related congenital muscular dystrophy; LMNA-RM, LMNA-related myopathies; sIBM, sporadic inclusion body myositis; TLR, Toll-like receptor
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spelling pubmed-70001402020-02-19 Up-regulation of Toll-like receptors 7 and 9 and its potential implications in the pathogenic mechanisms of LMNA-related myopathies Cappelletti, Cristina Salerno, Franco Canioni, Eleonora Mora, Marina Mantegazza, Renato Bernasconi, Pia Maggi, Lorenzo Nucleus Special Issue on Laminopathies Laminopathies are a heterogeneous group of diseases, caused by mutations in lamin A/C proteins. The most common laminopathy (LMNA-related myopathies, LMNA-RM) affects skeletal and cardiac muscles; muscle histopathology is variable, ranging from mild unspecific changes to dystrophic features, sometimes with inflammatory evidence. Whether the genetic defect might activate innate immune components, leading to chronic inflammation, myofiber necrosis and fibrosis, is still unknown. By qPCR, a significant up-regulation of Toll-like receptor (TLR) 7 and 9 transcripts was found in LMNA-RM compared to other myopathic and non-myopathic muscles. A marked TLR7/9 staining was observed on LMNA-RM blood vessels and muscle fibers and, when present, on infiltrating cells, mainly macrophages, scattered in the tissue or localized close to degenerated muscle fibers and connective tissue. Our results recognize innate immunity as a player in LMNA-RM pathogenesis. Modulation of TLR7/9 signaling pathways and decrease of macrophage-mediated inflammation might be potential therapeutic strategies in LMNA-RM management. Abbreviations: DMD, Duchenne muscular dystrophy; EDMD2, Emery-Dreifuss muscular dystrophy type 2; FSHD, facio-scapulo-humeral muscular dystrophy; LGMD1B, limb-girdle muscular dystrophy type 1B; LMNA-CMD, LMNA-related congenital muscular dystrophy; LMNA-RM, LMNA-related myopathies; sIBM, sporadic inclusion body myositis; TLR, Toll-like receptor Taylor & Francis 2018-10-03 /pmc/articles/PMC7000140/ /pubmed/29895224 http://dx.doi.org/10.1080/19491034.2018.1471947 Text en © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Special Issue on Laminopathies
Cappelletti, Cristina
Salerno, Franco
Canioni, Eleonora
Mora, Marina
Mantegazza, Renato
Bernasconi, Pia
Maggi, Lorenzo
Up-regulation of Toll-like receptors 7 and 9 and its potential implications in the pathogenic mechanisms of LMNA-related myopathies
title Up-regulation of Toll-like receptors 7 and 9 and its potential implications in the pathogenic mechanisms of LMNA-related myopathies
title_full Up-regulation of Toll-like receptors 7 and 9 and its potential implications in the pathogenic mechanisms of LMNA-related myopathies
title_fullStr Up-regulation of Toll-like receptors 7 and 9 and its potential implications in the pathogenic mechanisms of LMNA-related myopathies
title_full_unstemmed Up-regulation of Toll-like receptors 7 and 9 and its potential implications in the pathogenic mechanisms of LMNA-related myopathies
title_short Up-regulation of Toll-like receptors 7 and 9 and its potential implications in the pathogenic mechanisms of LMNA-related myopathies
title_sort up-regulation of toll-like receptors 7 and 9 and its potential implications in the pathogenic mechanisms of lmna-related myopathies
topic Special Issue on Laminopathies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000140/
https://www.ncbi.nlm.nih.gov/pubmed/29895224
http://dx.doi.org/10.1080/19491034.2018.1471947
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