骨骼肌纤维类型受到诸多内分泌信号及转录因子调节。研究发现，成纤维细胞生长因子21（FGF21）参与骨骼肌卫星细胞分化和肌纤维类型决定的调控。申请者前期工作表明，FGF21可能通过ERK/mTORC1信号网络促进小鼠成肌细胞向慢肌纤维分化，但内在分子机制尚不清楚。基于此，本项目拟首先在猪骨骼肌卫星细胞中超表达或干扰FGF21，探明其调控肌卫星细胞成肌分化和肌纤维形成过程中ERK1/2磷酸化和mTORC1通路活性的变化。继而通过抑制剂对ERK1/2及mTORC1信号分子进行干预，利用免疫共沉淀、磷酸化蛋白质组学和RNAi等技术验证ERK1/2与mTORC1蛋白复合物的相互作用并明晰信号网络。最后，结合动物试验，阐明FGF21对猪肌纤维发育和类型组成的调节效应及ERK/mTORC1信号介导机制。本项目研究结果将明晰猪骨骼肌纤维类型决定的内分泌调控网络，可为研发猪肉品质改良技术提供新的理论依据。

Muscle fiber types are regulated by many endocrine signals and transcriptional factors. Studies showed that fibroblast growth factor 21 (FGF21) plays an important role in the regulation of skeletal muscle satellite cell differentiation and muscle fiber-type determination. We previously found that FGF21 may promote formation of slow muscle fibers through the ERK/mTORC1 signaling network, yet the underlying precise mechanism remains unclear. Based on this, firstly porcine FGF21 over-expression and knocking-down satellite cells will be established to explore the effect of FGF21 on satellite cells myogenic differentiation and muscle fiber formation, as well as the expression of ERK1/2 phosphorylation and mTORC1 activity. Secondly, after blocking ERK1/2 or mTORC1 signaling with inhibitors in porcine FGF21 over-expression satellite cells, we will further verify the interaction between ERK1/2 and mTORC1 complex, and elucidate the associated signaling network using Co-immunoprecipitation, phosphoproteomics and RNA interference technologies. Finally, in vivo, we will investigate the mechanism of FGF21 regulating skeletal muscle development and muscle fiber type composition in pigs through ERK/mTORC1 signaling. The findings of the current project could clarify the endocrine regulatory network of porcine muscle fiber-type determination, and provide the new theoretical basis for developing technique to improve pork quality.