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Anti-Differentiation Effect of Oncogenic Met Receptor in Terminally-Differentiated Myotubes

Activation of the hepatocyte growth factor/Met receptor is involved in muscle regeneration, through promotion of proliferation and inhibition of differentiation in myogenic stem cells (MSCs). We previously described that the specific expression of an oncogenic version of the Met receptor (Tpr–Met) i...

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Autores principales: Sala, Valentina, Gallo, Simona, Gatti, Stefano, Vigna, Elisa, Ponzetto, Antonio, Crepaldi, Tiziana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344230/
https://www.ncbi.nlm.nih.gov/pubmed/28536403
http://dx.doi.org/10.3390/biomedicines3010124
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author Sala, Valentina
Gallo, Simona
Gatti, Stefano
Vigna, Elisa
Ponzetto, Antonio
Crepaldi, Tiziana
author_facet Sala, Valentina
Gallo, Simona
Gatti, Stefano
Vigna, Elisa
Ponzetto, Antonio
Crepaldi, Tiziana
author_sort Sala, Valentina
collection PubMed
description Activation of the hepatocyte growth factor/Met receptor is involved in muscle regeneration, through promotion of proliferation and inhibition of differentiation in myogenic stem cells (MSCs). We previously described that the specific expression of an oncogenic version of the Met receptor (Tpr–Met) in terminally-differentiated skeletal muscle causes muscle wasting in vivo. Here, we induced Tpr–Met in differentiated myotube cultures derived from the transgenic mouse. These cultures showed a reduced protein level of myosin heavy chain (MyHC), increased phosphorylation of Erk1,2 MAPK, the formation of giant sacs of myonuclei and the collapse of elongated myotubes. Treatment of the cultures with an inhibitor of the MAPK kinase pathway or with an inhibitor of the proteasome increased the expression levels of MyHC. In addition, the inhibition of the MAPK kinase pathway prevented the formation of myosacs and myotube collapse. Finally, we showed that induction of Tpr–Met in primary myotubes was unable to produce endoreplication in their nuclei. In conclusion, our data indicate that multinucleated, fused myotubes may be forced to disassemble their contractile apparatus by the Tpr–Met oncogenic factor, but they resist the stimulus toward the reactivation of the cell cycle.
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spelling pubmed-53442302017-05-23 Anti-Differentiation Effect of Oncogenic Met Receptor in Terminally-Differentiated Myotubes Sala, Valentina Gallo, Simona Gatti, Stefano Vigna, Elisa Ponzetto, Antonio Crepaldi, Tiziana Biomedicines Article Activation of the hepatocyte growth factor/Met receptor is involved in muscle regeneration, through promotion of proliferation and inhibition of differentiation in myogenic stem cells (MSCs). We previously described that the specific expression of an oncogenic version of the Met receptor (Tpr–Met) in terminally-differentiated skeletal muscle causes muscle wasting in vivo. Here, we induced Tpr–Met in differentiated myotube cultures derived from the transgenic mouse. These cultures showed a reduced protein level of myosin heavy chain (MyHC), increased phosphorylation of Erk1,2 MAPK, the formation of giant sacs of myonuclei and the collapse of elongated myotubes. Treatment of the cultures with an inhibitor of the MAPK kinase pathway or with an inhibitor of the proteasome increased the expression levels of MyHC. In addition, the inhibition of the MAPK kinase pathway prevented the formation of myosacs and myotube collapse. Finally, we showed that induction of Tpr–Met in primary myotubes was unable to produce endoreplication in their nuclei. In conclusion, our data indicate that multinucleated, fused myotubes may be forced to disassemble their contractile apparatus by the Tpr–Met oncogenic factor, but they resist the stimulus toward the reactivation of the cell cycle. MDPI 2015-02-12 /pmc/articles/PMC5344230/ /pubmed/28536403 http://dx.doi.org/10.3390/biomedicines3010124 Text en © 2015 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sala, Valentina
Gallo, Simona
Gatti, Stefano
Vigna, Elisa
Ponzetto, Antonio
Crepaldi, Tiziana
Anti-Differentiation Effect of Oncogenic Met Receptor in Terminally-Differentiated Myotubes
title Anti-Differentiation Effect of Oncogenic Met Receptor in Terminally-Differentiated Myotubes
title_full Anti-Differentiation Effect of Oncogenic Met Receptor in Terminally-Differentiated Myotubes
title_fullStr Anti-Differentiation Effect of Oncogenic Met Receptor in Terminally-Differentiated Myotubes
title_full_unstemmed Anti-Differentiation Effect of Oncogenic Met Receptor in Terminally-Differentiated Myotubes
title_short Anti-Differentiation Effect of Oncogenic Met Receptor in Terminally-Differentiated Myotubes
title_sort anti-differentiation effect of oncogenic met receptor in terminally-differentiated myotubes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344230/
https://www.ncbi.nlm.nih.gov/pubmed/28536403
http://dx.doi.org/10.3390/biomedicines3010124
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