Epigenetics and muscle dysfunction in chronic obstructive pulmonary disease

  • Esther Barreiro
    Reprint requests: Esther Barreiro, Pulmonology Department and Lung Cancer Research Group, IMIM-Hospital del Mar, PRBB, Dr Aiguader, 88, E-08003 Barcelona, Spain
    Respiratory Medicine Department-Muscle and Respiratory System Research Unit, Institute of Medical Research of Hospital del Mar (IMIM)-Hospital del Mar, Parc de Salut Mar, Barcelona Biomedical Research Park (PRBB), Barcelona, Spain

    Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
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  • Joaquim Gea
    Respiratory Medicine Department-Muscle and Respiratory System Research Unit, Institute of Medical Research of Hospital del Mar (IMIM)-Hospital del Mar, Parc de Salut Mar, Barcelona Biomedical Research Park (PRBB), Barcelona, Spain

    Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
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Published:April 17, 2014DOI:
      Chronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable disease and a major leading cause of morbidity and mortality worldwide. In COPD, comorbidities, acute exacerbations, and systemic manifestations negatively influence disease severity and progression regardless of the respiratory condition. Skeletal muscle dysfunction, which is one of the commonest systemic manifestations in patients with COPD, has a tremendous impact on their exercise capacity and quality of life. Several pathophysiological and molecular underlying mechanisms including epigenetics (the process whereby gene expression is regulated by heritable mechanisms that do not affect DNA sequence) have been shown to participate in the etiology of COPD muscle dysfunction. The epigenetic modifications identified so far in cells include DNA methylation, histone acetylation and methylation, and noncoding RNAs such as microRNAs. Herein, we first review the role of epigenetic mechanisms in muscle development and adaptation to environmental factors in several models. Moreover, the epigenetic events reported so far to be potentially involved in muscle dysfunction and mass loss of patients with COPD are also discussed. Furthermore, the different expression profile of several muscle-enriched microRNAs in the diaphragm and vastus lateralis muscles of patients with COPD are also reviewed from results recently obtained in our group. The role of protein hyperacetylation in enhanced muscle protein catabolism of limb muscles is also discussed. Future research should focus on the full elucidation of the triggers of epigenetic mechanisms and their specific downstream biological pathways in COPD muscle dysfunction and wasting.


      ANOVA (Analysis of variance), COPD (chronic obstructive pulmonary disease), MyHC (myosin heavy chain), CH3 (methyl group), coA (coenzyme A), CpG (cytosine and guanosine nucleotides), DNA (deoxyribonucleic acid), HSP (heat shock proteins), HTAs (histone acetyltransferases), HDACs (histone deacetylases), H3K4me3 (histone H3 trimethyl Lys4), Hox-A11 (homeobox A11), IGF-1 (insulin-like growth factor-1), NAD (nicotinamide adenine dinucleotide), PHD (plant homeodomains), MRTF (myocardin-related transcription factors), MEF2 (myocyte-enhancing factor), Myf-5 (myogenic factor 5), pax7 (paired box protein), PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha), SRF (serum response factor), TGF (transforming growth factor), RNA (ribonucleic acid), RISC (RNA-induced silencing complex), SIRT (sirtuin), YY1 (Yin Yang 1)
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