Skeletal Muscle Remodelling as a Function of Disease Progression in Amyotrophic Lateral Sclerosis
Muscle weakness is considered the pivotal sign of amyotrophic lateral sclerosis (ALS). Knowledge about the skeletal muscle degeneration/regeneration process and the myogenic potential is limited in ALS patients. Therefore, we investigate these processes in a time course perspective by analysing skel...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852332/ https://www.ncbi.nlm.nih.gov/pubmed/27195289 http://dx.doi.org/10.1155/2016/5930621 |
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author | Jensen, L. Jørgensen, L. H. Bech, R. D. Frandsen, U. Schrøder, H. D. |
author_facet | Jensen, L. Jørgensen, L. H. Bech, R. D. Frandsen, U. Schrøder, H. D. |
author_sort | Jensen, L. |
collection | PubMed |
description | Muscle weakness is considered the pivotal sign of amyotrophic lateral sclerosis (ALS). Knowledge about the skeletal muscle degeneration/regeneration process and the myogenic potential is limited in ALS patients. Therefore, we investigate these processes in a time course perspective by analysing skeletal muscle biopsies from ALS patients collected before and after a 12-week period of normal daily activities and compare these with healthy age-matched control tissue. We do this by evaluating mRNA and protein (immunohistochemical) markers of regeneration, neurodegeneration, myogenesis, cell cycle regulation, and inflammation. Our results show morphological changes indicative of active denervation and reinnervation and an increase in small atrophic fibres. We demonstrate differences between ALS and controls in pathways controlling skeletal muscle homeostasis, cytoskeletal and regenerative markers, neurodegenerative factors, myogenic factors, cell cycle determinants, and inflammatory markers. Our results on Pax7 and MyoD protein expression suggest that proliferation and differentiation of skeletal muscle stem cells are affected in ALS patients, and the myogenic processes cannot overcome the denervation-induced wasting. |
format | Online Article Text |
id | pubmed-4852332 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-48523322016-05-18 Skeletal Muscle Remodelling as a Function of Disease Progression in Amyotrophic Lateral Sclerosis Jensen, L. Jørgensen, L. H. Bech, R. D. Frandsen, U. Schrøder, H. D. Biomed Res Int Research Article Muscle weakness is considered the pivotal sign of amyotrophic lateral sclerosis (ALS). Knowledge about the skeletal muscle degeneration/regeneration process and the myogenic potential is limited in ALS patients. Therefore, we investigate these processes in a time course perspective by analysing skeletal muscle biopsies from ALS patients collected before and after a 12-week period of normal daily activities and compare these with healthy age-matched control tissue. We do this by evaluating mRNA and protein (immunohistochemical) markers of regeneration, neurodegeneration, myogenesis, cell cycle regulation, and inflammation. Our results show morphological changes indicative of active denervation and reinnervation and an increase in small atrophic fibres. We demonstrate differences between ALS and controls in pathways controlling skeletal muscle homeostasis, cytoskeletal and regenerative markers, neurodegenerative factors, myogenic factors, cell cycle determinants, and inflammatory markers. Our results on Pax7 and MyoD protein expression suggest that proliferation and differentiation of skeletal muscle stem cells are affected in ALS patients, and the myogenic processes cannot overcome the denervation-induced wasting. Hindawi Publishing Corporation 2016 2016-04-18 /pmc/articles/PMC4852332/ /pubmed/27195289 http://dx.doi.org/10.1155/2016/5930621 Text en Copyright © 2016 L. Jensen et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Jensen, L. Jørgensen, L. H. Bech, R. D. Frandsen, U. Schrøder, H. D. Skeletal Muscle Remodelling as a Function of Disease Progression in Amyotrophic Lateral Sclerosis |
title | Skeletal Muscle Remodelling as a Function of Disease Progression in Amyotrophic Lateral Sclerosis |
title_full | Skeletal Muscle Remodelling as a Function of Disease Progression in Amyotrophic Lateral Sclerosis |
title_fullStr | Skeletal Muscle Remodelling as a Function of Disease Progression in Amyotrophic Lateral Sclerosis |
title_full_unstemmed | Skeletal Muscle Remodelling as a Function of Disease Progression in Amyotrophic Lateral Sclerosis |
title_short | Skeletal Muscle Remodelling as a Function of Disease Progression in Amyotrophic Lateral Sclerosis |
title_sort | skeletal muscle remodelling as a function of disease progression in amyotrophic lateral sclerosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852332/ https://www.ncbi.nlm.nih.gov/pubmed/27195289 http://dx.doi.org/10.1155/2016/5930621 |
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