Imperial College London
Alternate

ProfessorJaneMitchell

Faculty of Medicine, National Heart & Lung Institute

Professor of Pharmacology in Critical Care Medicine
 
 
 
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Contact

 

+44 (0)20 7351 8137j.a.mitchell

 
 
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Assistant

 

Ms Lisa Quinn +44 (0)20 7594 1345

 
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Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ciano:2019:10.1038/s41598-019-45567-4,
author = {Ciano, M and Mantellato, G and Connolly, M and Paul-Clark, M and Mitchell, J and Wilson-Owen, S and Cookson, W and Moffatt, M and Hughes, S and Polkey, M and Kemp, P and Natanek, S},
doi = {10.1038/s41598-019-45567-4},
journal = {Scientific Reports},
title = {EGF receptor (EGFR) inhibition promotes a slow-twitch oxidative, over a fast-twitch, muscle phenotype},
url = {http://dx.doi.org/10.1038/s41598-019-45567-4},
volume = {9},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Ciano,M
AU  - Mantellato,G
AU  - Connolly,M
AU  - Paul-Clark,M
AU  - Mitchell,J
AU  - Wilson-Owen,S
AU  - Cookson,W
AU  - Moffatt,M
AU  - Hughes,S
AU  - Polkey,M
AU  - Kemp,P
AU  - Natanek,S
DO  - 10.1038/s41598-019-45567-4
PY  - 2019///
SN  - 2045-2322
TI  - EGF receptor (EGFR) inhibition promotes a slow-twitch oxidative, over a fast-twitch, muscle phenotype
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/s41598-019-45567-4
UR  - http://hdl.handle.net/10044/1/70194
VL  - 9
ER  -
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