title: Epigenetic regulation of muscle phenotype and adaptation: a potential role in COPD muscle dysfunction.
abstract: Quadriceps muscle dysfunction occurs in one-third of patients with chronic obstructive pulmonary disease (COPD) in very early stages of their condition, even prior to the development of airway obstruction. Among several factors, deconditioning and muscle mass loss are the most relevant contributing factors leading to this dysfunction. Moreover, epigenetics, defined as the process whereby gene expression is regulated by heritable mechanisms that do not affect DNA sequence, could be involved in the susceptibility to muscle dysfunction, pathogenesis, and progression. Herein, we review the role of epigenetic mechanisms in muscle development and adaptation to environmental factors such as immobilization and exercise, and their implications in the pathophysiology and susceptibility to muscle dysfunction in COPD. The epigenetic modifications identified so far include DNA methylation, histone acetylation and methylation, and non-coding RNAs such as microRNAs (miRNAs). In the present review, we describe the specific contribution of epigenetic mechanisms to the regulation of embryonic myogenesis, muscle structure and metabolism, immobilization, and exercise, and in muscles of COPD patients. Events related to muscle development and regeneration and the response to exercise and immobilization are tightly regulated by epigenetic mechanisms. These environmental factors play a key role in the outcome of muscle mass and function as well as in the susceptibility to muscle dysfunction in COPD. Future research remains to be done to shed light on the specific target pathways of miRNA function and other epigenetic mechanisms in the susceptibility, pathogenesis, and progression of COPD muscle dysfunction.
authors.affiliation: Respiratory Medicine Department-Lung Cancer Research Group, Institute of Medical Research of Hospital del Mar (IMIMHospital del Mar, Barcelona Biomedical Research Park (PRBB Barcelona, Spain. ebarreiro@imim.es
authors.forename: Esther
authors.initials: E
authors.lastname: Barreiro
authors.forename: Jacob I
authors.initials: JI
authors.lastname: Sznajder
mesh_terms: D000222:Adaptation, Physiological; D044127:Epigenesis, Genetic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D024510:Muscle Development / Q000235:genetics; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000503:physiopathology*; D052097:Quadriceps Muscle / Q000503:physiopathology*
chemical_list: D035683:MicroRNAs
keywords: chronic obstructive pulmonary disease; epigenetics; muscle adaptation; muscle dysfunction; myogenesis