Department of Bioagricultural Sciences, National Chiayi University, No. 300 Syuefu Rd., Chiayi 60004, Taiwan, ROC.
Mol Cell Biochem. 2012 Jun;365(1-2):251-62. doi: 10.1007/s11010-012-1266-2. Epub 2012 Feb 26.
Previous studies have shown that Wnt signaling is involved in postnatal mammalian myogenesis; however, the downstream mechanism of Wnt signaling is not fully understood. This study reports that the murine four-and-a-half LIM domain 1 (Fhl1) could be stimulated by β-catenin or LiCl treatment to induce myogenesis. In contrast, knockdown of the Fhl1 gene expression in C2C12 cells led to reduced myotube formation. We also adopted reporter assays to demonstrate that either β-catenin or LiCl significantly activated the Fhl1 promoter, which contains four putative consensus TCF/LEF binding sites. Mutations of two of these sites caused a significant decrease in promoter activity by luciferase reporter assay. Thus, we suggest that Wnt signaling induces muscle cell differentiation, at least partly, through Fhl1 activation.
先前的研究表明 Wnt 信号通路参与了哺乳动物出生后的肌发生过程；然而，Wnt 信号通路的下游机制尚未完全阐明。本研究报道了β-catenin 或 LiCl 处理可激活鼠类四半胱氨酸结构域 1（Fhl1），从而诱导肌发生。相反，在 C2C12 细胞中敲低 Fhl1 基因表达会导致肌管形成减少。我们还采用报告基因检测证明，β-catenin 或 LiCl 均可显著激活含有四个潜在的 TCF/LEF 结合位点的 Fhl1 启动子。荧光素酶报告基因检测显示，两个位点的突变会导致启动子活性显著降低。因此，我们认为 Wnt 信号通路至少部分通过 Fhl1 的激活诱导肌肉细胞分化。
