TIEG1 Negatively Controls the Myoblast Pool Indispensable for Fusion During Myogenic Differentiation of C2C12 Cells
TIEG1 Negatively Controls the Myoblast Pool Indispensable for Fusion During Myogenic Differentiation of C2C12 Cells
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DOI：
10.1002/jcp.22434
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发表时间：
2011-04-01
影响因子：
5.6
通讯作者：
Yamaguchi, Takahiro
中科院分区：
文献类型：
--
作者：
Miyake, Masato;Hayashi, Shinichiro;Yamaguchi, Takahiro
转化生长因子（TGF）-β诱导型早期基因（TIEG）-1与某些细胞类型中细胞增殖、分化和凋亡的控制有关。由于TIEG 1的功能可能与TGF-β（肌生成的抑制因子）相关，因此TIEG 1也可能参与肌生成。因此，我们使用小鼠成肌细胞系C2 C12研究了TIEG 1在体外成肌分化过程中的功能。在C2 C12细胞分化过程中，TIEG 1表达增加。TIEG 1的组成型表达降低了存活率并减少了肌管形成。相反，敲低TIEG 1表达增加了分化过程中活细胞的数量，并加速成肌细胞融合成多核肌管。然而，成肌分化标记物肌细胞生成素的表达不受TIEG 1敲低的影响。这些事件的机制进行了研究，重点是成肌细胞的数量诱导分化后的调节。TIEG 1的敲低导致细胞周期状态的变化和在分化的初始阶段的细胞凋亡的抑制。基因芯片和实时荧光PCR分析表明，TIEG 1基因敲低的细胞中细胞周期进程的调节因子高度表达。因此，TIEG 1是成肌细胞库的负调节因子，其导致肌原分化期间肌管形成的抑制。J.细胞。226：1128-1136，2011。(C)2010 Wiley-Liss，Inc.
The transforming growth factor (TGF)-beta inducible early gene (TIEG)-1 is implicated in the control of cell proliferation, differentiation, and apoptosis in some cell types. Since TIEG1 functioning may be associated with TGF-beta, a suppressor of myogenesis, TIEG1 is also likely to be involved in myogenesis. Therefore, we investigated the function of TIEG1 during myogenic differentiation in vitro using the murine myoblasts cell line, C2C12. TIEG1 expression increased during differentiation of C2C12 cells. Constitutive expression of TIEG1 reduced survival and decreased myotube formation. Conversely, knocking down TIEG1 expression increased the number of viable cells during differentiation, and accelerated myoblast fusion into multinucleated myotubes. However, expression of the myogenic differentiation marker, myogenin, remained unaffected by TIEG1 knockdown. The mechanism underlying these events was investigated by focusing on the regulation of myoblast numbers after induction of differentiation. The knockdown of TIEG1 led to changes in cell cycle status and inhibition of apoptosis during the initial stages of differentiation. Microarray and real-time PCR analyses showed that the regulators of cell cycle progression were highly expressed in TIEG1 knockdown cells. Therefore, TIEG1 is a negative regulator of the myoblast pool that causes inhibition of myotube formation during myogenic differentiation. J. Cell. Physiol. 226: 1128-1136, 2011. (C) 2010 Wiley-Liss, Inc.