成肌细胞融合对骨骼肌发育至关重要,增长,和再生。然而,成肌细胞融合和分化的分子机制尚不完全清楚。以前,我们报道了白细胞介素-4(IL-4)促进成肌细胞融合;因此,我们假设IL-4信号可能调节参与成肌细胞融合的分子的表达。在这项研究中,我们证明了除了融合,IL-4通过诱导成肌细胞测定蛋白1(MyoD)和肌原蛋白促进C2C12成肌细胞分化,两者都调节Myommer和Myomaker的表达,成肌细胞融合所必需的膜蛋白。出乎意料的是,IL-4处理增加了肌体的表达,但不是Myomaker,在C2C12细胞中。通过小干扰RNA敲低C2C12细胞中IL-4受体α(IL-4Rα),损害成肌细胞融合和分化。我们还证明了MyoD表达的减少,Myogenin,通过敲低C2C12细胞中的IL-4Rα,而Myomaker的表达水平保持不变。最后,细胞混合测定和肌体表达的恢复部分挽救了IL-4Rα敲低C2C12细胞中受损的融合。总的来说,这些结果表明,IL-4/IL-4Rα轴通过诱导成肌调节因子促进成肌细胞的融合和分化,MyoD和肌生成素,还有Myomerger.
Myoblast fusion is essential for skeletal muscle development, growth, and regeneration. However, the molecular mechanisms underlying myoblast fusion and differentiation are not fully understood. Previously, we reported that interleukin-4 (IL-4) promotes myoblast fusion; therefore, we hypothesized that IL-4 signaling might regulate the expression of the molecules involved in myoblast fusion. In this study, we showed that in addition to fusion, IL-4 promoted the differentiation of C2C12 myoblast cells by inducing myoblast determination protein 1 (MyoD) and myogenin, both of which regulate the expression of myomerger and myomaker, the membrane proteins essential for myoblast fusion. Unexpectedly, IL-4 treatment increased the expression of myomerger, but not myomaker, in C2C12 cells. Knockdown of IL-4 receptor alpha (IL-4Rα) in C2C12 cells by small interfering RNA impaired myoblast fusion and differentiation. We also demonstrated a reduction in the expression of MyoD, myogenin, and myomerger by knockdown of IL-4Rα in C2C12 cells, while the expression level of myomaker remained unchanged. Finally, cell mixing assays and the restoration of myomerger expression partially rescued the impaired fusion in the IL-4Rα-knockdown C2C12 cells. Collectively, these results suggest that the IL-4/IL-4Rα axis promotes myoblast fusion and differentiation via the induction of myogenic regulatory factors, MyoD and myogenin, and myomerger.