State Key Laboratory of Biocontrol, School of Life Science, Sun Yat-Sen University, Guangzhou 510006, PR China.
Gene. 2013 Dec 15;532(2):263-71. doi: 10.1016/j.gene.2013.08.088. Epub 2013 Sep 11.
Tmod4 (Tropomodulin 4) is a member of Tmod family that plays important role in thin filament length regulation and myofibril assembly. We found that the expression levels of Tmod4 were higher in skeletal muscle and adipose tissues. However, the function and regulation of the Tmod4 gene in the myogenesis and adipogenesis remains unclear. In this study, we found that the expression of Tmod4 was decreased in myogenesis while increased in adipogenesis. Then, the transcriptional regulation analysis of Tmod4 promoter showed that Tmod4 could be regulated directly by myogenic factors and adipogenic factors. Furthermore, the roles of Tmod4 in the myogenesis and adipogenesis were confirmed by its over-expression in C2C12 cells and 3T3 cells, which suggested that Tmod4 could promote adipogenesis by up-regulating the adipogenic factors but moderately delay the myogenesis. These results indicated that the Tmod4 gene may play as a switch between myogenesis and adipogenesis, which resulted in the balanced development between skeletal muscle and adipose tissue. Therefore, the model for switch role of the Tmod4 in the balanced regulation between myogenesis and adipogenesis was proposed. It is showed that the expression of Tmod4 was activated in adipogenesis by adipogenic factors while inhibited in myogenesis by myogenic factors. Moreover, Tmod4 could promote adipogenesis by up-regulating the expression of adipogenic factors while moderately delaying the myogenesis. Our study provides an important basis for further understanding the regulation and function of porcine Tmod4 in muscle and fat development.
Tmod4（Tropomodulin 4）是 Tropomodulin 家族的成员，在细肌丝长度调节和肌原纤维组装中发挥重要作用。我们发现 Tmod4 在骨骼肌和脂肪组织中的表达水平较高。然而，Tmod4 基因在肌发生和脂肪发生中的功能和调节仍不清楚。在这项研究中，我们发现 Tmod4 在肌发生过程中的表达降低，而在脂肪发生过程中的表达增加。然后，对 Tmod4 启动子的转录调控分析表明，Tmod4 可以被肌源性和脂肪源性因子直接调节。此外，通过在 C2C12 细胞和 3T3 细胞中转染 Tmod4 过表达，证实了 Tmod4 在肌发生和脂肪发生中的作用，这表明 Tmod4 可以通过上调脂肪生成因子促进脂肪生成，但适度延缓肌发生。这些结果表明，Tmod4 基因可能在肌发生和脂肪发生之间起着“开关”的作用，导致骨骼肌和脂肪组织的平衡发育。因此，提出了 Tmod4 在肌发生和脂肪发生平衡调节中作为开关的作用模型。结果表明，脂肪生成因子激活脂肪生成过程中 Tmod4 的表达，而肌源性因子抑制肌发生过程中 Tmod4 的表达。此外，Tmod4 可以通过上调脂肪生成因子的表达来促进脂肪生成，同时适度延迟肌发生。我们的研究为进一步了解猪 Tmod4 在肌肉和脂肪发育中的调节和功能提供了重要依据。
