Abstract：
Skeletal muscle is crucial for animal movement and posture maintenance, and it serves as a significant source of meat in the livestock and poultry industry. The number of muscle fibers differentiated from myoblast in the embryonic stage is one of the factors determining the content of skeletal muscle. Insulin-like growth factor 2 (IGF2), a well-known growth-promoting hormone, is crucial for embryonic and skeletal muscle growth and development. However, the specific molecular mechanism underlying its impact on chicken embryonic myoblast differentiation remains unclear. To elucidate the molecular mechanism by which IGF2 regulates chicken myoblast differentiation, we manipulated IGF2 expression in chicken embryonic myoblast. The results demonstrated that IGF2 was upregulated during chicken skeletal muscle development and myoblast differentiation. On the one hand, we found that IGF2 promotes mitochondrial biogenesis through the PGC1/NRF1/TFAM pathway, thereby enhancing mitochondrial membrane potential, oxidative phosphorylation, and ATP synthesis during myoblast differentiation. This process is mediated by the PI3K/AKT pathway. On the other hand, IGF2 regulates BNIP3-mediated mitophagy, clearing dysfunctional mitochondria. Collectively, our findings confirmed that IGF2 cooperatively regulates mitochondrial biogenesis and mitophagy to remodel the mitochondrial network and enhance mitochondrial function, ultimately promoting myoblast differentiation.
摘要：
骨骼肌对于动物的运动和姿势保持至关重要，它是畜牧业和家禽业的重要肉类来源。在胚胎阶段从成肌细胞分化的肌纤维的数量是决定骨骼肌含量的因素之一。胰岛素样生长因子2(IGF2),一种众所周知的促生长激素,对胚胎和骨骼肌的生长和发育至关重要。然而,其影响鸡胚成肌细胞分化的具体分子机制尚不清楚。阐明IGF2调控鸡成肌细胞分化的分子机制,我们操纵了IGF2在鸡胚成肌细胞中的表达。结果表明，IGF2在鸡骨骼肌发育和成肌细胞分化过程中上调。一方面,我们发现IGF2通过PGC1/NRF1/TFAM途径促进线粒体生物发生，从而增强线粒体膜电位，氧化磷酸化，和成肌细胞分化过程中的ATP合成。这一进程由PI3K/AKT通路介导。另一方面,IGF2调节BNIP3介导的线粒体自噬，清除功能失调的线粒体。总的来说，我们的研究结果证实，IGF2协同调节线粒体生物发生和线粒体自噬重塑线粒体网络，增强线粒体功能，最终促进成肌细胞分化。
