Possible role of TIEG1 as a feedback regulator of myostatin and TGF-β in myoblasts
Possible role of TIEG1 as a feedback regulator of myostatin and TGF-β in myoblasts
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DOI：
10.1016/j.bbrc.2010.02.077
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发表时间：
2010-03-19
影响因子：
3.1
通讯作者：
Yamaguchi, Takahiro
中科院分区：
文献类型：
--
作者：
Miyake, Masato;Hayashi, Shinichiro;Yamaguchi, Takahiro
肌生长抑制素和TGF-β负调节骨骼肌的发育和生长。这两种因子都通过Smad 2/3途径进行信号传导。然而，肌肉生长抑制素和TGF-β信号转导的调节机制仍不清楚。TGF-β诱导早期基因（TIEG）1在骨骼肌中高度表达，并参与TGF-β信号转导的调节。这些发现促使我们使用C2 C12成肌细胞研究TIEG 1对肌生长抑制素和TGF-β信号传导的影响。在增殖的C2 C12细胞中，肌生长抑制素和TGF-β诱导TIEG 1和Smad 7 mRNA的表达，但不诱导TIEG 2 mRNA的表达。当分化的C2 C12成肌细胞被肌肉生长抑制素刺激时，TIEG 1 mRNA在分化的晚期被上调。相反，TGF-β在早期阶段增强TIEG 1表达。TIEG 1的过表达阻止了在增殖或分化的C2 C12细胞中肌生长抑制素和TGF-β对Smad的转录激活，但Smad 2和Smad 7 mRNA的表达不受影响。TIEG 1的强制表达抑制了肌源性分化，但在肌生长抑制素或TGF-β存在下，并没有引起比空载体更多的抑制。这些结果表明，TIEG 1是一种可能的肌生长抑制素和TGF-β的反馈调节剂，防止成肌细胞中的过度作用。(C)2010年爱思唯尔公司All rights reserved.
Myostatin and TGF-beta negatively regulate skeletal muscle development and growth. Both factors signal through the Smad2/3 pathway. However, the regulatory mechanism of myostatin and TGF-beta signaling remains unclear. TGF-beta inducible early gene (TIEG) 1 is highly expressed in skeletal muscle and has been implicated in the modulation of TGF-beta signaling. These findings prompted us to investigate the effect of TIEG1 on myostatin and TGF-beta signaling using C2C12 myoblasts. Myostatin and TGF-beta induced the expression of TIEG1 and Smad7 mRNAs, but not TIEG2 mRNA, in proliferating C2C12 cells. When differentiating C2C12 myoblasts were stimulated by myostatin, TIEG1 mRNA was up-regulated at a late stage of differentiation. In contrast, TGF-beta enhanced TIEG1 expression at an early stage. Overexpression of TIEG1 prevented the transcriptional activation of Smad by myostatin and TGF-beta in both proliferating or differentiating C2C12 cells, but the expression of Smad2 and Smad7 mRNAs was not affected. Forced expression of TIEG1 inhibited myogenic differentiation but did not cause more inhibition than the empty vector in the presence of myostatin or TGF-beta. These results demonstrate that TIEG1 is one possible feedback regulator of myostatin and TGF-beta that prevents excess action in myoblasts. (C) 2010 Elsevier Inc. All rights reserved.