TY - JOUR
T1 - TGF-β Regulates Collagen Type I Expression in Myoblasts and Myotubes via Transient Ctgf and Fgf-2 Expression
AU - Hillege, Michèle M. G.
AU - Galli Caro, Ricardo A.
AU - Offringa, Carla
AU - de Wit, Gerard M. J.
AU - Hoogaars, Willem M. H.
AU - Jaspers, Richard T.
N1 - Special Issue: Muscle Homeostasis and Regeneration: From Molecular Mechanisms to Therapeutic Opportunities.
PY - 2020/2/6
Y1 - 2020/2/6
N2 - 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.
AB - 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.
KW - Acvr1b
KW - Col1a1
KW - Tgfbr1
KW - atrophy
KW - fibrosis
KW - myogenesis
KW - myostatin
KW - skeletal muscle
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85085897674&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/32041253
UR - http://www.scopus.com/inward/record.url?scp=85085897674&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85085897674&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/cells9020375
DO - https://doi.org/10.3390/cells9020375
M3 - Article
C2 - 32041253
SN - 2073-4409
VL - 9
SP - 1
EP - 21
JO - Cells
JF - Cells
IS - 2
M1 - 375
ER -
