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dc.contributor.authorLewis, Aen_US
dc.contributor.authorRiddoch-Contreras, Jen_US
dc.contributor.authorNatanek, SAen_US
dc.contributor.authorDonaldson, Aen_US
dc.contributor.authorMan, WD-Cen_US
dc.contributor.authorMoxham, Jen_US
dc.contributor.authorHopkinson, NSen_US
dc.contributor.authorPolkey, MIen_US
dc.contributor.authorKemp, PRen_US
dc.date.accessioned2015-09-22T10:32:04Z
dc.date.issued2012-01en_US
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/8807
dc.descriptionThis is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the licenseen_US
dc.description.abstractRATIONALE: Muscle atrophy confers a poor prognosis in patients with chronic obstructive pulmonary disease (COPD), yet the molecular pathways responsible are poorly characterised. Muscle-specific microRNAs and serum response factor (SRF) are important regulators of muscle phenotype that contribute to a feedback system to regulate muscle gene expression. The role of these factors in the skeletal muscle dysfunction that accompanies COPD is unknown. METHODS: 31 patients with COPD and 14 healthy age-matched controls underwent lung and quadriceps function assessments, measurement of daily activity and a percutaneous quadriceps muscle biopsy. The expression of muscle-specific microRNAs, myosin heavy chains and components of the serum response factor signalling pathway were determined by qPCR. RESULTS: A reduction in expression of miR-1 (2.5-fold, p=0.01) and the myocardin-related transcription factors (MRTFs) A and B was observed in patients compared with controls (MRTF-A mRNA: twofold, p=0.028; MRTF-B mRNA: fourfold, p=0.011). miR-1 expression was associated with smoking history, lung function, fat-free mass index, 6 min walk distance and percentage of type 1 fibres. miR-133 and miR-206 were negatively correlated with daily physical activity. Insulin-like growth factor 1 mRNA was increased in the patients and miR-1 was negatively correlated with phosphorylation of the kinase Akt. Furthermore, the protein levels of histone deacetylase 4, another miR-1 target, were increased in the patients. CONCLUSIONS: Downregulation of the activity of the MRTF-SRF axis and the expression of muscle-specific microRNAs, particularly miR-1, may contribute to COPD-associated skeletal muscle dysfunction.en_US
dc.description.sponsorshipBBSRC, Wellcome Trust and the National Institute for Health Research (NIHR) Respiratory Biomedical Unit at the Royal Brompton Hospital and Imperial College. AL is a BBSRC PhD student, SAN received a Wellcome Trust Fellowship, AD received a NIHR Respiratory Biomedical Unit fellowship and WM is a NIHR Clinician Scientist. NSH is a HEFCE Clinical Senior Lecturer. MIP's salary is part funded by the NIHR Respiratory Biomedical Unit at the Royal Brompton Hospital and National Heart & Lung Institute.en_US
dc.format.extent26 - 34en_US
dc.languageengen_US
dc.language.isoenen_US
dc.relation.ispartofThoraxen_US
dc.subjectAgeden_US
dc.subjectBiopsyen_US
dc.subjectDisease Progressionen_US
dc.subjectDown-Regulationen_US
dc.subjectFemaleen_US
dc.subjectFluorescent Antibody Techniqueen_US
dc.subjectFollow-Up Studiesen_US
dc.subjectGenetic Predisposition to Diseaseen_US
dc.subjectHumansen_US
dc.subjectMaleen_US
dc.subjectMicroRNAsen_US
dc.subjectMuscular Diseasesen_US
dc.subjectPulmonary Disease, Chronic Obstructiveen_US
dc.subjectQuadriceps Muscleen_US
dc.subjectReverse Transcriptase Polymerase Chain Reactionen_US
dc.subjectSerum Response Factoren_US
dc.subjectSignal Transductionen_US
dc.titleDownregulation of the serum response factor/miR-1 axis in the quadriceps of patients with COPD.en_US
dc.typeArticle
dc.identifier.doi10.1136/thoraxjnl-2011-200309en_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/21998125en_US
pubs.issue1en_US
pubs.notesNot knownen_US
pubs.publication-statusPublisheden_US
pubs.volume67en_US


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