Segregation of myoblast fusion and muscle-specific gene expression by distinct ligand-dependent inactivation of GSK-3β.

Segregation of myoblast fusion and muscle-specific gene expression by distinct ligand-dependent inactivation of GSK-3β.
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DOI:
10.1007/s00018-010-0467-7
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发表时间:
2011-02
影响因子:
8
通讯作者:
Langen, R. C. J.
Langen, R. C. J.
中科院分区:
生物学1区
文献类型:
--
作者:
Pansters, N. A. M.;van der Velden, J. L. J.;Kelders, M. C. J. M.;Laeremans, H.;Schols, A. M. W. J.;Langen, R. C. J.

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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)、遗传学或IGF-I介导的GSK-3β失活的刺激。为了评估肌源性分化的刺激是否与配体介导的GSK-3β失活共同,研究了响应Wnt-3a的成肌细胞融合和肌肉特异性基因表达。此外,评估了IGF-I/GSK-3β/NFATc 3和Wnt/GSK-3β/β-连环蛋白信号传导之间的串扰。虽然Wnt-3a和LiCl都促进成肌细胞融合,但LiCl增加了肌肉特异性基因表达,而Wnt-3a或β-连环蛋白过表达则没有增加。此外,LiCl和IGF-I,而不是Wnt-3a,增加NFATc 3转录活性。相比之下,Wnt-3a和LiCl增加了β-连环蛋白依赖的转录活性,但IGF-I没有增加。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途径刺激成肌细胞分化后,成肌细胞融合和肌肉特异性基因表达的分离调节。本文的在线版本(doi:10.1007/s 00018 -010-0467-7)包含补充材料,可供授权用户使用。
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. The online version of this article (doi:10.1007/s00018-010-0467-7) contains supplementary material, which is available to authorized users.
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