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Meta-analysis of expression signatures of muscle atrophy: gene interaction networks in early and late stages
BACKGROUND: Skeletal muscle mass can be markedly reduced through a process called atrophy, as a consequence of many diseases or critical physiological and environmental situations. Atrophy is characterised by loss of contractile proteins and reduction of fiber volume. Although in the last decade the...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2642825/ https://www.ncbi.nlm.nih.gov/pubmed/19108710 http://dx.doi.org/10.1186/1471-2164-9-630 |
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author | Calura, Enrica Cagnin, Stefano Raffaello, Anna Laveder, Paolo Lanfranchi, Gerolamo Romualdi, Chiara |
author_facet | Calura, Enrica Cagnin, Stefano Raffaello, Anna Laveder, Paolo Lanfranchi, Gerolamo Romualdi, Chiara |
author_sort | Calura, Enrica |
collection | PubMed |
description | BACKGROUND: Skeletal muscle mass can be markedly reduced through a process called atrophy, as a consequence of many diseases or critical physiological and environmental situations. Atrophy is characterised by loss of contractile proteins and reduction of fiber volume. Although in the last decade the molecular aspects underlying muscle atrophy have received increased attention, the fine mechanisms controlling muscle degeneration are still incomplete. In this study we applied meta-analysis on gene expression signatures pertaining to different types of muscle atrophy for the identification of novel key regulatory signals implicated in these degenerative processes. RESULTS: We found a general down-regulation of genes involved in energy production and carbohydrate metabolism and up-regulation of genes for protein degradation and catabolism. Six functional pathways occupy central positions in the molecular network obtained by the integration of atrophy transcriptome and molecular interaction data. They are TGF-β pathway, apoptosis, membrane trafficking/cytoskeleton organization, NFKB pathways, inflammation and reorganization of the extracellular matrix. Protein degradation pathway is evident only in the network specific for muscle short-term response to atrophy. TGF-β pathway plays a central role with proteins SMAD3/4, MYC, MAX and CDKN1A in the general network, and JUN, MYC, GNB2L1/RACK1 in the short-term muscle response network. CONCLUSION: Our study offers a general overview of the molecular pathways and cellular processes regulating the establishment and maintenance of atrophic state in skeletal muscle, showing also how the different pathways are interconnected. This analysis identifies novel key factors that could be further investigated as potential targets for the development of therapeutic treatments. We suggest that the transcription factors SMAD3/4, GNB2L1/RACK1, MYC, MAX and JUN, whose functions have been extensively studied in tumours but only marginally in muscle, appear instead to play important roles in regulating muscle response to atrophy. |
format | Text |
id | pubmed-2642825 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-26428252009-02-17 Meta-analysis of expression signatures of muscle atrophy: gene interaction networks in early and late stages Calura, Enrica Cagnin, Stefano Raffaello, Anna Laveder, Paolo Lanfranchi, Gerolamo Romualdi, Chiara BMC Genomics Research Article BACKGROUND: Skeletal muscle mass can be markedly reduced through a process called atrophy, as a consequence of many diseases or critical physiological and environmental situations. Atrophy is characterised by loss of contractile proteins and reduction of fiber volume. Although in the last decade the molecular aspects underlying muscle atrophy have received increased attention, the fine mechanisms controlling muscle degeneration are still incomplete. In this study we applied meta-analysis on gene expression signatures pertaining to different types of muscle atrophy for the identification of novel key regulatory signals implicated in these degenerative processes. RESULTS: We found a general down-regulation of genes involved in energy production and carbohydrate metabolism and up-regulation of genes for protein degradation and catabolism. Six functional pathways occupy central positions in the molecular network obtained by the integration of atrophy transcriptome and molecular interaction data. They are TGF-β pathway, apoptosis, membrane trafficking/cytoskeleton organization, NFKB pathways, inflammation and reorganization of the extracellular matrix. Protein degradation pathway is evident only in the network specific for muscle short-term response to atrophy. TGF-β pathway plays a central role with proteins SMAD3/4, MYC, MAX and CDKN1A in the general network, and JUN, MYC, GNB2L1/RACK1 in the short-term muscle response network. CONCLUSION: Our study offers a general overview of the molecular pathways and cellular processes regulating the establishment and maintenance of atrophic state in skeletal muscle, showing also how the different pathways are interconnected. This analysis identifies novel key factors that could be further investigated as potential targets for the development of therapeutic treatments. We suggest that the transcription factors SMAD3/4, GNB2L1/RACK1, MYC, MAX and JUN, whose functions have been extensively studied in tumours but only marginally in muscle, appear instead to play important roles in regulating muscle response to atrophy. BioMed Central 2008-12-23 /pmc/articles/PMC2642825/ /pubmed/19108710 http://dx.doi.org/10.1186/1471-2164-9-630 Text en Copyright © 2008 Calura et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Calura, Enrica Cagnin, Stefano Raffaello, Anna Laveder, Paolo Lanfranchi, Gerolamo Romualdi, Chiara Meta-analysis of expression signatures of muscle atrophy: gene interaction networks in early and late stages |
title | Meta-analysis of expression signatures of muscle atrophy: gene interaction networks in early and late stages |
title_full | Meta-analysis of expression signatures of muscle atrophy: gene interaction networks in early and late stages |
title_fullStr | Meta-analysis of expression signatures of muscle atrophy: gene interaction networks in early and late stages |
title_full_unstemmed | Meta-analysis of expression signatures of muscle atrophy: gene interaction networks in early and late stages |
title_short | Meta-analysis of expression signatures of muscle atrophy: gene interaction networks in early and late stages |
title_sort | meta-analysis of expression signatures of muscle atrophy: gene interaction networks in early and late stages |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2642825/ https://www.ncbi.nlm.nih.gov/pubmed/19108710 http://dx.doi.org/10.1186/1471-2164-9-630 |
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