Differential regulation of IGF-I and IGF-II gene expression in skeletal muscle cells
Differential regulation of IGF-I and IGF-II gene expression in skeletal muscle cells
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DOI：
10.1007/s11010-012-1479-4
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发表时间：
2013-01-01
影响因子：
4.3
通讯作者：
Lu, Ling
中科院分区：
文献类型：
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作者：
Jiao, Shuang;Ren, Hongxia;Lu, Ling
胰岛素样生长因子（IGF）-I和IGF-II在骨骼肌生长和分化的调节中起主要作用，并且两者都在肌细胞中局部表达。最近的研究表明，IGF-II在肌肉发生过程中上调其自身的基因表达，这种自调节回路对肌肉分化至关重要。在这一过程中，当地IGF-I是如何调节的尚不清楚。在这里，我们报告说，虽然IGF-II上调其自身的基因表达，它抑制IGF-I基因表达在肌发生。IGF-II对IGF-I和IGF-II基因表达的这些相反作用具有时间依赖性和剂量依赖性。已经显示IGFs激活PI 3 K-Akt-mTOR、p38 MAPK和Erk 1/2 MAPK通路。在成肌细胞中，我们研究了它们在介导IGF-II相反作用中的作用。我们的研究结果表明，PI 3 K-Akt-mTOR和p38 MAPK通路在增加IGF-II mRNA表达中起关键作用。相反，mTOR是IGF-II下调IGF-I基因表达所必需的。此外，Akt、Erk 1/2 MAPK和p38 MAPK通路也参与了肌形成过程中IGF-I和IGF-II基因基础水平的调节。这些发现揭示了一种以前未被认识的负反馈机制，并扩展了我们对IGF-I和IGF-II基因表达和调控的认识。
Insulin-like growth factor (IGF)-I and IGF-II play major roles in the regulation of skeletal muscle growth and differentiation, and both are locally expressed in muscle cells. Recent studies have demonstrated that IGF-II up-regulates its own gene expression during myogenesis and this auto-regulatory loop is critical for muscle differentiation. How local IGF-I is regulated in this process is unclear. Here, we report that while IGF-II up-regulated its own gene expression, it suppressed IGF-I gene expression during myogenesis. These opposite effects of IGF-II on IGF-I and IGF-II genes expression were time dependent and dose dependent. It has been shown that IGFs activate the PI3K-Akt-mTOR, p38 MAPK, and Erk1/2 MAPK pathways. In myoblasts, we examined their role(s) in mediating the opposite effects of IGF-II. Our results showed that both the PI3K-Akt-mTOR and p38 MAPK pathways played critical roles in increasing IGF-II mRNA expression. In contrast, mTOR was required for down-regulating the IGF-I gene expression by IGF-II. In addition, Akt, Erk1/2 MAPK, and p38 MAPK pathways were also involved in the regulation of basal levels of IGF-I and IGF-II genes during myogenesis. These findings reveal a previously unrecognized negative feedback mechanism and extend our knowledge of IGF-I and IGF-II gene expression and regulation during myogenesis.