TGF-β Regulates Collagen Type I Expression in Myoblasts and Myotubes via Transient <i>Ctgf</i> and <i>Fgf-2</i> Expression
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 myotu...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-02-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/9/2/375 |
| id |
doaj-1ced9a20c5474ed5ad75b0efd4925e6a |
|---|---|
| record_format |
Article |
| spelling |
doaj-1ced9a20c5474ed5ad75b0efd4925e6a2020-11-25T02:16:09ZengMDPI AGCells2073-44092020-02-019237510.3390/cells9020375cells9020375TGF-β Regulates Collagen Type I Expression in Myoblasts and Myotubes via Transient <i>Ctgf</i> and <i>Fgf-2</i> ExpressionMichèle M. G. Hillege0Ricardo A. Galli Caro1Carla Offringa2Gerard M. J. de Wit3Richard T. Jaspers4Willem M. H. Hoogaars5Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, 1081 BT Amsterdam, The NetherlandsLaboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, 1081 BT Amsterdam, The NetherlandsLaboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, 1081 BT Amsterdam, The NetherlandsLaboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, 1081 BT Amsterdam, The NetherlandsLaboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, 1081 BT Amsterdam, The NetherlandsLaboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, 1081 BT Amsterdam, The NetherlandsTransforming 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 <i>Myh3</i> expression was observed. In both myoblasts and myotubes, TGF-β acutely induced the expression of a subset of genes involved in fibrosis, such as <i>Ctgf</i> and <i>Fgf-2,</i> which was subsequently followed by increased expression of <i>Col1a1</i>. Knockdown of <i>Ctgf</i> and <i>Fgf-2</i> resulted in a lower <i>Col1a1</i> 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 <i>Tgfbr1</i>, but not receptor <i>Acvr1b,</i> resulted in a reduction in <i>Ctgf</i> and <i>Col1a1</i> expression. These results indicate that, during muscle regeneration, TGF-β induces fibrosis via <i>Tgfbr1</i> by stimulating the autocrine signalling of <i>Ctgf</i> and <i>Fgf-2.</i>https://www.mdpi.com/2073-4409/9/2/375<i>acvr1b</i><i>tgfbr1</i>myostatin<i>col1a1</i>skeletal musclefibrosismyogenesisatrophy |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Michèle M. G. Hillege Ricardo A. Galli Caro Carla Offringa Gerard M. J. de Wit Richard T. Jaspers Willem M. H. Hoogaars |
| spellingShingle |
Michèle M. G. Hillege Ricardo A. Galli Caro Carla Offringa Gerard M. J. de Wit Richard T. Jaspers Willem M. H. Hoogaars TGF-β Regulates Collagen Type I Expression in Myoblasts and Myotubes via Transient <i>Ctgf</i> and <i>Fgf-2</i> Expression Cells <i>acvr1b</i> <i>tgfbr1</i> myostatin <i>col1a1</i> skeletal muscle fibrosis myogenesis atrophy |
| author_facet |
Michèle M. G. Hillege Ricardo A. Galli Caro Carla Offringa Gerard M. J. de Wit Richard T. Jaspers Willem M. H. Hoogaars |
| author_sort |
Michèle M. G. Hillege |
| title |
TGF-β Regulates Collagen Type I Expression in Myoblasts and Myotubes via Transient <i>Ctgf</i> and <i>Fgf-2</i> Expression |
| title_short |
TGF-β Regulates Collagen Type I Expression in Myoblasts and Myotubes via Transient <i>Ctgf</i> and <i>Fgf-2</i> Expression |
| title_full |
TGF-β Regulates Collagen Type I Expression in Myoblasts and Myotubes via Transient <i>Ctgf</i> and <i>Fgf-2</i> Expression |
| title_fullStr |
TGF-β Regulates Collagen Type I Expression in Myoblasts and Myotubes via Transient <i>Ctgf</i> and <i>Fgf-2</i> Expression |
| title_full_unstemmed |
TGF-β Regulates Collagen Type I Expression in Myoblasts and Myotubes via Transient <i>Ctgf</i> and <i>Fgf-2</i> Expression |
| title_sort |
tgf-β regulates collagen type i expression in myoblasts and myotubes via transient <i>ctgf</i> and <i>fgf-2</i> expression |
| publisher |
MDPI AG |
| series |
Cells |
| issn |
2073-4409 |
| publishDate |
2020-02-01 |
| description |
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 <i>Myh3</i> expression was observed. In both myoblasts and myotubes, TGF-β acutely induced the expression of a subset of genes involved in fibrosis, such as <i>Ctgf</i> and <i>Fgf-2,</i> which was subsequently followed by increased expression of <i>Col1a1</i>. Knockdown of <i>Ctgf</i> and <i>Fgf-2</i> resulted in a lower <i>Col1a1</i> 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 <i>Tgfbr1</i>, but not receptor <i>Acvr1b,</i> resulted in a reduction in <i>Ctgf</i> and <i>Col1a1</i> expression. These results indicate that, during muscle regeneration, TGF-β induces fibrosis via <i>Tgfbr1</i> by stimulating the autocrine signalling of <i>Ctgf</i> and <i>Fgf-2.</i> |
| topic |
<i>acvr1b</i> <i>tgfbr1</i> myostatin <i>col1a1</i> skeletal muscle fibrosis myogenesis atrophy |
| url |
https://www.mdpi.com/2073-4409/9/2/375 |
| work_keys_str_mv |
AT michelemghillege tgfbregulatescollagentypeiexpressioninmyoblastsandmyotubesviatransientictgfiandifgf2iexpression AT ricardoagallicaro tgfbregulatescollagentypeiexpressioninmyoblastsandmyotubesviatransientictgfiandifgf2iexpression AT carlaoffringa tgfbregulatescollagentypeiexpressioninmyoblastsandmyotubesviatransientictgfiandifgf2iexpression AT gerardmjdewit tgfbregulatescollagentypeiexpressioninmyoblastsandmyotubesviatransientictgfiandifgf2iexpression AT richardtjaspers tgfbregulatescollagentypeiexpressioninmyoblastsandmyotubesviatransientictgfiandifgf2iexpression AT willemmhhoogaars tgfbregulatescollagentypeiexpressioninmyoblastsandmyotubesviatransientictgfiandifgf2iexpression |
| _version_ |
1724892408478433280 |