Foxol represses expression of musclin, a skeletal muscle-derived secretory factor
Foxol represses expression of musclin, a skeletal muscle-derived secretory factor
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DOI：
10.1016/j.bbrc.2007.10.013
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发表时间：
2007-12-14
影响因子：
3.1
通讯作者：
Shimomura, Iichiro
中科院分区：
文献类型：
--
作者：
Yasui, Atsutaka;Nishizawa, Hitoshi;Shimomura, Iichiro
肌肉素是一种新的骨骼肌源性分泌因子，其mRNA水平受营养状态的显著调节。在本研究中，我们研究了胰岛素对musclin mRNA的调节机制。在C2 C12心肌细胞中，胰岛素诱导的musclin mRNA的上调被磷脂酰肌醇3-激酶（PI 3 K）抑制剂LY 294002显著降低，并且在稳定表达组成型活性Foxo 1（Foxo 1-3A）的C2 C12心肌细胞中被消除，这表明Foxo I参与了musclin mRNA的调节。musclin启动子缺失分析表明，-303/-123区域是Foxol抑制musclin启动子活性的重要区域。染色质免疫沉淀实验表明Foxol与musclin启动子结合。Foxol转基因小鼠腓肠肌Musclin mRNA水平显著下调。我们的研究结果表明，Foxol下调musclin mRNA的表达在体外和体内，这应该解释胰岛素介导的上调该基因在肌肉细胞。(C)2007爱思唯尔公司All rights reserved.
Musclin is a novel skeletal muscle-derived secretory factor, whose mRNA level is markedly regulated by nutritional status. In the present study, we investigated the mechanism of musclin mRNA regulation by insulin. In C2C12 myocytes, insulin-induced upregulation of musclin mRNA was significantly decreased by treatment of phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, and was abolished in C2C12 myocytes stably expressing a constitutively active Foxo 1 (Foxo 1-3A), suggesting the involvement of Foxo I in the regulation of musclin mRNA. Promoter deletion analysis of musclin promoter revealed that the region of -303/-123 is important for the repression of promoter activity by Foxol. Chromatin immunoprecipitation assay showed that Foxol bound to musclin promoter. Musclin mRNA level was markedly downregulated in gastrocnemius muscle of Foxol transgenic mice. Our results demonstrated that Foxol downregulates musclin mRNA expression both in vitro and in vivo, which should explain insulin-mediated upregulation of this gene in muscle cells. (C) 2007 Elsevier Inc. All rights reserved.