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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

IMPACT FACTOR 2017: 3.022

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Volume 399, Issue 3


TGF-β requires the activation of canonical and non-canonical signalling pathways to induce skeletal muscle atrophy

Johanna Ábrigo
  • Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas and Facultad de Medicina, Universidad Andres Bello, Avenida República 239, Santiago 8370146, Chile
  • Millennium Institute on Immunology and Immunotherapy, 8331150 Santiago, Chile
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/ Fabian Campos
  • Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas and Facultad de Medicina, Universidad Andres Bello, Avenida República 239, Santiago 8370146, Chile
  • Millennium Institute on Immunology and Immunotherapy, 8331150 Santiago, Chile
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/ Felipe Simon
  • Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas and Facultad de Medicina, Universidad Andres Bello, Avenida República 239, Santiago 8370146, Chile
  • Millennium Institute on Immunology and Immunotherapy, 8331150 Santiago, Chile
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/ Claudia Riedel
  • Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas and Facultad de Medicina, Universidad Andres Bello, Avenida República 239, Santiago 8370146, Chile
  • Millennium Institute on Immunology and Immunotherapy, 8331150 Santiago, Chile
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/ Daniel Cabrera
  • Universidad Bernardo O Higgins, Facultad de Salud, Departamento de Ciencias Químicas y Biológicas, 8370993 Santiago, Chile
  • Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, 8331150 Santiago, Chile
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/ Cristian Vilos
  • Laboratory of Nanomedicine and Targeted Delivery, Center for Integrative Medicine and Innovative Science, Faculty of Medicine, and Center for Bioinformatics and Integrative Biology, Faculty of Biological Sciences, Universidad Andres Bello, 8370146 Santiago, Chile
  • Center for the Development of Nanoscience and Nanotechnology (CEDENNA), Universidad de Santiago de Chile, 9170022 Santiago, Chile
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/ Claudio Cabello-Verrugio
  • Corresponding author
  • Millennium Institute on Immunology and Immunotherapy, 8331150 Santiago, Chile
  • Laboratory of Muscle Pathology, Fragility and Aging, Departmento de Ciencias Biológicas, Facultad de Ciencias Biológicas and Facultad de Medicina, Universidad Andres Bello, Avenida República 239, Santiago 8370146, Chile
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Published Online: 2017-11-15 | DOI: https://doi.org/10.1515/hsz-2017-0217


The transforming growth factor type-beta (TGF-β) induces skeletal muscle atrophy characterised by a decrease in the fibre’s diameter and levels of myosin heavy chain (MHC), also as an increase of MuRF-1 expression. In addition, TGF-β induces muscle atrophy by a mechanism dependent on reactive oxygen species (ROS). TGF-β signals by activating both canonical Smad-dependent, and non-canonical signalling pathways such as ERK1/2, JNK1/2, and p38 MAPKs. However, the participation of canonical and non-canonical signalling pathways in the TGF-β atrophic effect on skeletal muscle is unknown. We evaluate the impact of Smad and MAPK signalling pathways on the TGF-β-induced atrophic effect in C2C12 myotubes. The results indicate that TGF-β activates Smad2/3, ERK1/2 and JNK1/2, but not p38 in myotubes. The pharmacological inhibition of Smad3, ERK1/2 and JNK1/2 activation completely abolished the atrophic effect of TGF-β. Finally, the inhibition of these canonical and non-canonical pathways did not decrease the ROS increment, while the inhibition of ROS production entirely abolished the phosphorylation of Smad3, ERK1/2 and JNK1/2. These results suggest that TGF-β requires Smad3, ERK1/2 and JNK1/2 activation to produce skeletal muscle atrophy. Moreover, the induction of ROS by TGF-β is an upstream event to canonical and non-canonical pathways.

This article offers supplementary material which is provided at the end of the article.

Keywords: MAPK; MuRF-1; muscle atrophy; reactive oxygen species; Smad


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About the article

Received: 2017-08-11

Accepted: 2017-11-03

Published Online: 2017-11-15

Published in Print: 2018-02-23

Citation Information: Biological Chemistry, Volume 399, Issue 3, Pages 253–264, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2017-0217.

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