College of Animal Science and Technology, Ningxia University, Yinchuan, 750021, China.
Institute of Physical Education, Yan'an University, Yan'an, 716000, China.
Funct Integr Genomics. 2023 May 30;23(2):191. doi: 10.1007/s10142-023-01115-y.
As a key component of Transforming growth factor-β (TGF-β) pathway, Smad2 has many crucial roles in a variety of cellular processes, but it cannot bind DNA without complex formation with Smad4. In the present study, the molecular mechanism in the progress of myogenesis underlying transcriptional regulation of SMAD2 and SMAD4 had been clarified. The result showed the inhibition between SMAD2 and SMAD4, which promotes and inhibits bovine myoblast differentiation, respectively. Further, the characterization of promoter region of SMAD2 and SMAD4 was analyzed, and identified C/EBPβ directly bound to the core region of both SMAD2 and SMAD4 genes promoter and stimulated the transcriptional activity. However, C/EBPβ has lower expression in myoblasts which plays vital function in the transcriptional networks controlling adipogenesis, while the overexpression of C/EBPβ gene in myoblasts significantly increased SMAD2 and SMAD4 gene expression, induced the formation of lipid droplet in bovine myoblasts, and promoted the expression of adipogenesis-specific genes. Collectively, our results showed that C/EBPβ may play an important role in the trans-differentiation and dynamic equilibrium of myoblasts into adipocyte cells via promoting an increase in SMAD2 and SMAD4 gene levels. These results will provide an important basis for further understanding of the TGFβ pathway and C/EBPβ gene during myogenic differentiation.
作为转化生长因子-β（TGF-β）途径的关键组成部分，Smad2 在多种细胞过程中具有许多关键作用，但它不能在与 Smad4 形成复合物的情况下结合 DNA。在本研究中，阐明了 SMAD2 和 SMAD4 转录调控下肌发生过程中的分子机制。结果表明，SMAD2 和 SMAD4 之间存在抑制作用，分别促进和抑制牛肌细胞分化。此外，还分析了 SMAD2 和 SMAD4 启动子区域的特征，并鉴定出 C/EBPβ 直接结合到 SMAD2 和 SMAD4 基因启动子的核心区域，并刺激转录活性。然而，C/EBPβ 在肌细胞中的表达较低，它在控制脂肪生成的转录网络中起着至关重要的作用，而 C/EBPβ 基因在肌细胞中的过表达显著增加了 SMAD2 和 SMAD4 基因的表达，诱导牛肌细胞中脂滴的形成，并促进脂肪生成特异性基因的表达。总的来说，我们的结果表明，C/EBPβ 可能通过增加 SMAD2 和 SMAD4 基因水平在肌细胞向脂肪细胞的转分化和动态平衡中发挥重要作用。这些结果将为进一步理解 TGFβ 途径和 C/EBPβ 基因在肌生成分化过程中提供重要依据。
