Department of Respiratory Medicine, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, The Netherlands.
Cell Mol Life Sci. 2011 Feb;68(3):523-35. doi: 10.1007/s00018-010-0467-7. Epub 2010 Aug 8.
Myogenic differentiation involves myoblast fusion and induction of muscle-specific gene expression, which are both stimulated by pharmacological (LiCl), genetic, or IGF-I-mediated GSK-3β inactivation. To assess whether stimulation of myogenic differentiation is common to ligand-mediated GSK-3β inactivation, myoblast fusion and muscle-specific gene expression were investigated in response to Wnt-3a. Moreover, crosstalk between IGF-I/GSK-3β/NFATc3 and Wnt/GSK-3β/β-catenin signaling was assessed. While both Wnt-3a and LiCl promoted myoblast fusion, muscle-specific gene expression was increased by LiCl, but not by Wnt-3a or β-catenin over-expression. Furthermore, LiCl and IGF-I, but not Wnt-3a, increased NFATc3 transcriptional activity. In contrast, β-catenin-dependent transcriptional activity was increased by Wnt-3a and LiCl, but not IGF-I. These results for the first time reveal a segregated regulation of myoblast fusion and muscle-specific gene expression following stimulation of myogenic differentiation in response to distinct ligand-specific signaling routes of GSK-3β inactivation.
成肌分化涉及成肌细胞融合和肌肉特异性基因表达的诱导，这两者都受到药理学（LiCl）、遗传或 IGF-I 介导的 GSK-3β失活的刺激。为了评估配体介导的 GSK-3β失活是否普遍存在于刺激成肌分化中，研究了 Wnt-3a 对成肌细胞融合和肌肉特异性基因表达的影响。此外，还评估了 IGF-I/GSK-3β/NFATc3 和 Wnt/GSK-3β/β-catenin 信号通路之间的串扰。虽然 Wnt-3a 和 LiCl 都促进了成肌细胞融合，但 LiCl 增加了肌肉特异性基因表达，而 Wnt-3a 或 β-catenin 过表达则没有。此外，LiCl 和 IGF-I 但不是 Wnt-3a 增加了 NFATc3 的转录活性。相比之下，β-catenin 依赖性转录活性增加了 Wnt-3a 和 LiCl，但不是 IGF-I。这些结果首次揭示了在响应 GSK-3β失活的不同配体特异性信号通路刺激成肌分化后，成肌细胞融合和肌肉特异性基因表达的分离调控。
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