EGF receptor (EGFR) inhibition promotes a slow-twitch oxidative, over a fast-twitch, muscle phenotype

File Description SizeFormat 
Accepted version SREP EGFR paper.pdfFile embargoed until 01 January 10000125.83 kBAdobe PDF    Request a copy
Fig 1 PDF.pdfFile embargoed until 01 January 10000427.66 kBAdobe PDF    Request a copy
Fig 2 PDF.pdfFile embargoed until 01 January 10000915.04 kBAdobe PDF    Request a copy
Fig 3 PDF.pdfFile embargoed until 01 January 10000959.98 kBAdobe PDF    Request a copy
Title: EGF receptor (EGFR) inhibition promotes a slow-twitch oxidative, over a fast-twitch, muscle phenotype
Authors: Ciano, M
Mantellato, G
Connolly, M
Paul-Clark, M
Mitchell, J
Wilson-Owen, S
Cookson, W
Moffatt, M
Hughes, S
Polkey, M
Kemp, P
Natanek, S
Item Type: Journal Article
Abstract: A low quadriceps slow-twitch (ST), oxidative (relative to fast-twitch) fiber proportion is prevalent in chronic diseases such Chronic Obstructive Pulmonary Disease (COPD) and is associated with exercise limitation and poor outcomes. Benefits of an increased ST fiber proportion are demonstrated in genetically modified animals. Pathway analysis of published data of differentially expressed genes in mouse ST and FT fibers, mining of our microarray data and a qPCR analysis of quadriceps specimens from COPD patients and controls were performed. ST markers were quantified in C2C12 myotubes with EGF-neutralizing antibody, EGFR inhibitor or an EGFR-silencing RNA added. A zebrafish egfra mutant was generated by genome editing and ST fibers counted. EGF signaling was (negatively) associated with the ST muscle phenotype in mice and humans, and muscle EGF transcript levels were raised in COPD. In C2C12 myotubes, EGFR inhibition/silencing increased ST, including mitochondrial, markers. In zebrafish, egfra depletion increased ST fibers and mitochondrial content. EGF is negatively associated with ST muscle phenotype in mice, healthy humans and COPD patients. EGFR blockade promotes the ST phenotype in myotubes and zebrafish embryos. EGF signaling suppresses the ST phenotype, therefore EGFR inhibitors may be potential treatments for COPD-related muscle ST fiber loss.
Issue Date: 25-Jun-2019
Date of Acceptance: 10-Apr-2019
URI: http://hdl.handle.net/10044/1/70194
ISSN: 2045-2322
Publisher: Nature Publishing Group
Journal / Book Title: Scientific Reports
Copyright Statement: This paper is embargoed until publication. Once published it will be available fully open access.
Publication Status: Accepted
Embargo Date: publication subject to indefinite embargo
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commons