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Cited by 74Muscle Physiology and DisordersChronic Obstructive Pulmonary Disease (COPD) ResearchBioinformatics and Genomic Networks

A Systems Biology Approach Identifies Molecular Networks Defining Skeletal Muscle Abnormalities in Chronic Obstructive Pulmonary Disease

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Turan, Nil, Kalko, Susana, Stincone, Anna, Clarke, Kim, Sabah, Ayesha, Howlett, Katherine, Curnow, S. John, Rodriguez, Diego A. +5 more·2011·PLoS Computational Biology
DOI 10.1371/journal.pcbi.1002129PMC PMC3164707
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Abstract

Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators. Our model shows that failure to co-ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles. Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization. These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients.

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  • Hypoxia seems to play a prominent role in the skeletal muscle wasting of COPD patients, as suggested by transcriptomic studies evidencing upregulation of four histone deacetylases in the muscle of COPD patients compared to healthy subjects and correlated with oxygen availability.

    “Hypoxia seems to play a prominent role in the skeletal muscle wasting of COPD patients, as suggested by a network-analysis transcriptomic studies evidencing upregulation of four histone deacetylase in the muscle of COPD patients (HDAC 9 and 4, SIRT 2 and 3) compared to that of healthy subjects and correlated with oxygen availability [66].”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [66]

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Authors
Turan, N., Kalko, S., Stincone, A., Clarke, K., Sabah, A., Howlett, K., Curnow, S. J., Rodriguez, D. A., Cascante, M., O'Neill, L., Egginton, S., Roca, J., & Falciani, F.
Affiliations
  • University of Birmingham (GB)
  • Hospital Clínic de Barcelona (ES)
  • Institut de Biomedicina de la Universitat de Barcelona (ES)
ORCID
Venue
PLoS Computational Biology
Publisher
Public Library of Science (PLoS)
Published
2011-09-01
Volume
7
Issue
9
Pages
e1002129
ISSN
  • 1553-734X (ISSN-L)
  • 1553-7358
DOI
10.1371/journal.pcbi.1002129
PMC
PMC3164707
OpenAlex
W2005659463
Cited by
74
References
66
Citations by year
2026: 3 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 5 · 2017: 4 · 2016: 3 · 2015: 10 · 2014: 23 · 2013: 8 · 2012: 3
FWCI
4.42
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Computational Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (publishedVersion, cc-by)
  • RECERCAT (Consorci de Serveis Universitaris de Catalunya) (publishedVersion, other-oa)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
Funders
  • European Commission (RD06/0020)
  • Generalitat de Catalunya (2009SGR1308, 2009SGR911, 2009-SGR-393)
  • Ministerio de Ciencia e Innovación (SAF2008-00164)
  • Instituto de Salud Carlos III (2009 SGR 911, RD06/0020, RD06/0020/0046, SAF2008-00164)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
Keywords
chronic obstructive pulmonary disease, skeletal muscle dysfunction, muscle degeneration, molecular networks, systemic inflammation, exercise training response, tissue remodeling, bioenergetics, histone modifiers, oxygen utilization, hypoxia, gene expression
MeSH terms
Aged, Animals, Energy Metabolism, Female, Histones, Humans, Male, Mice, Inbred C57BL, Middle Aged, Oxygen Consumption, RNA, Messenger, Cell Hypoxia, Up-Regulation, Cytokines, Muscle, Skeletal, Gene Expression Profiling, Pulmonary Disease, Chronic Obstructive, Systems Biology, Mice, Interleukin-1beta, Metabolic Networks and Pathways

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