Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, 1081 BT Amsterdam, The Netherlands.
Cells. 2020 Feb 6;9(2):375. doi: 10.3390/cells9020375.
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 expression was observed. In both myoblasts and myotubes, TGF-β acutely induced the expression of a subset of genes involved in fibrosis, such as and which was subsequently followed by increased expression of . Knockdown of and resulted in a lower 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 , but not receptor resulted in a reduction in and expression. These results indicate that, during muscle regeneration, TGF-β induces fibrosis via by stimulating the autocrine signalling of and
转化生长因子 β（TGF-β）不仅参与纤维化的调控，还参与肌肉质量的调控，并促进肌肉消耗性疾病的进行性病变。然而，关于 TGF-β在成肌细胞和肌管中的时间依赖性信号转导，以及 TGF-β如何影响 I 型胶原表达和这些细胞的表型，目前知之甚少。在这里，我们评估了 TGF-β在 C2C12 成肌细胞和肌管中 1、3、9、24 和 48 h 处理后的基因表达。在成肌细胞中，各种肌生成基因在 9、24 和 48 h 后受到抑制，而在肌管中仅观察到 表达减少。在成肌细胞和肌管中，TGF-β 急性诱导一组参与纤维化的基因表达，如 和 ，随后 表达增加。 和 的敲低导致 表达水平降低。此外，TGF-β 对肌生成和纤维化基因表达的影响比肌肉生长抑制素更为显著，并且 TGF-β 型 I 受体 的敲低，而不是受体 的敲低，导致 和 的表达减少。这些结果表明，在肌肉再生过程中，TGF-β 通过刺激 自分泌信号转导，诱导纤维化，从而导致
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