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

Johanna Ábrigo, Fabian Campos, Felipe Simon, Claudia Riedel, Daniel Cabrera, Cristian Vilos, Claudio Cabello-Verrugio

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)253-264
Number of pages12
JournalBiological Chemistry
Volume399
Issue number3
DOIs
Publication statusPublished - 23 Feb 2018

Keywords

  • MAPK
  • MuRF-1
  • muscle atrophy
  • reactive oxygen species
  • Smad

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry

Fingerprint

Dive into the research topics of 'TGF-β requires the activation of canonical and non-canonical signalling pathways to induce skeletal muscle atrophy'. Together they form a unique fingerprint.

Cite this