TGF-β Regulates Collagen Type I Expression in Myoblasts and Myotubes via Transient Ctgf and Fgf-2 Expression

Michèle M.G. Hillege, Ricardo A. Galli Caro, Carla Offringa, Gerard M.J. de Wit, Richard T. Jaspers, Willem M.H. Hoogaars

Research output: Contribution to JournalArticleAcademicpeer-review


Transforming Growth Factor β (TGF-β) is involved in fibrosis as well as the regulation of muscle mass, and contributes to the progressive pathology of muscle wasting disorders. However, little is known regarding the time-dependent signalling of TGF-β in myoblasts and myotubes, as well as how TGF-β affects collagen type I expression and the phenotypes of these cells. Here, we assessed effects of TGF-β on gene expression in C2C12 myoblasts and myotubes after 1, 3, 9, 24 and 48 h treatment. In myoblasts, various myogenic genes were repressed after 9, 24 and 48 h, while in myotubes only a reduction in Myh3 expression was observed. In both myoblasts and myotubes, TGF-β acutely induced the expression of a subset of genes involved in fibrosis, such as Ctgf and Fgf-2, which was subsequently followed by increased expression of Col1a1. Knockdown of Ctgf and Fgf-2 resulted in a lower Col1a1 expression level. Furthermore, the effects of TGF-β on myogenic and fibrotic gene expression were more pronounced than those of myostatin, and knockdown of TGF-β type I receptor Tgfbr1, but not receptor Acvr1b, resulted in a reduction in Ctgf and Col1a1 expression. These results indicate that, during muscle regeneration, TGF-β induces fibrosis via Tgfbr1 by stimulating the autocrine signalling of Ctgf and Fgf-2.

Original languageEnglish
Article number375
Pages (from-to)1-21
Number of pages21
Issue number2
Early online date6 Feb 2020
Publication statusPublished - Feb 2020

Bibliographical note

Special Issue: Muscle Homeostasis and Regeneration: From Molecular Mechanisms to Therapeutic Opportunities.


  • Acvr1b
  • atrophy
  • Col1a1
  • fibrosis
  • myogenesis
  • myostatin
  • skeletal muscle
  • Tgfbr1


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