Academic Journal

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

التفاصيل البيبلوغرافية
العنوان: EGF receptor (EGFR) inhibition promotes a slow-twitch oxidative, over a fast-twitch, muscle phenotype
المؤلفون: Ciano, Margherita, Mantellato, Giada, Connolly, Martin, Paul-Clark, Mark, Willis-Owen, Saffron, Moffatt, Miriam F, Cookson, William O C M, Mitchell, Jane A, Polkey, Michael I, Hughes, Simon M, Kemp, Paul R, Natanek, S Amanda
المصدر: Ciano , M , Mantellato , G , Connolly , M , Paul-Clark , M , Willis-Owen , S , Moffatt , M F , Cookson , W O C M , Mitchell , J A , Polkey , M I , Hughes , S M , Kemp , P R & Natanek , S A 2019 , ' EGF receptor (EGFR) inhibition promotes a slow-twitch oxidative, over a fast-twitch, muscle phenotype ' , Scientific Reports , vol. 9 , no. 1 , 9218 , pp. 9218 . https://doi.org/10.1038/s41598-019-45567-4
سنة النشر: 2019
المجموعة: King's College, London: Research Portal
الوصف: 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.
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
Relation: https://kclpure.kcl.ac.uk/portal/en/publications/3221109a-f558-4faf-a009-13bf6c775d25
DOI: 10.1038/s41598-019-45567-4
الاتاحة: https://kclpure.kcl.ac.uk/portal/en/publications/3221109a-f558-4faf-a009-13bf6c775d25
https://doi.org/10.1038/s41598-019-45567-4
https://kclpure.kcl.ac.uk/ws/files/112729347/s41598_019_45567_4.pdf
http://www.scopus.com/inward/record.url?scp=85068081704&partnerID=8YFLogxK
Rights: info:eu-repo/semantics/openAccess
رقم الانضمام: edsbas.E3B557C5
قاعدة البيانات: BASE
الوصف
DOI:10.1038/s41598-019-45567-4