Abstract：
What is the central question of this study? How are the dynamics of interleukin (IL)-15 and its receptors altered during the differentiation of myoblasts into myotubes, and how is IL-15 regulated? What is the main finding and its importance? The mRNA levels of IL-15 and interleukin-2 receptor subunits beta and gamma increase during skeletal muscle differentiation, whereas interleukin-15 receptor subunit alpha (IL-15RA) exhibits different kinetics. IL-15RA regulates the localization and expression of IL-15 at the protein level.
Interleukin-15 (IL-15) is a myokine in the interleukin-2 (IL-2) family that is generated in the skeletal muscle during exercise. The functional effect of IL-15 involves muscle regeneration and metabolic regulation in skeletal muscle. Reports have indicated that interleukin-15 receptor subunit alpha (IL-15RA) acts by regulating IL-15 localization in immune cells. However, the dynamics of IL-15 and its receptors, which regulate the IL-15 pathway in skeletal muscle differentiation, have not yet been clarified. In this study, we investigated the mechanism of IL-15 regulation using a mouse skeletal muscle cell line, C2C12 cells. We found that the mRNA expression of IL-15, interleukin-2 receptor subunit beta (IL-2RB; CD122) and interleukin-2 receptor subunit gamma (IL-2RG; CD132) increased, but that IL-15RA exhibited different kinetics as differentiation progressed. We also found that IL-15, mainly present in the cytosol, pre-assembled with IL-15RA in the cytosol and fused to the plasma membrane. Moreover, IL-15RA increased IL-15 protein levels. Our findings suggest that genes involved in the IL-15 signalling complex are enhanced with the differentiation of myotubes and that IL-15RA regulates the protein kinetics of IL-15 signalling in skeletal muscle.
Interleukin-15 (IL-15) is a myokine in the interleukin-2 (IL-2) family that is generated in the skeletal muscle during exercise. The functional effect of IL-15 involves muscle regeneration and metabolic regulation in skeletal muscle. Reports have indicated that interleukin-15 receptor subunit alpha (IL-15RA) acts by regulating IL-15 localization in immune cells. However, the dynamics of IL-15 and its receptors, which regulate the IL-15 pathway in skeletal muscle differentiation, have not yet been clarified. In this study, we investigated the mechanism of IL-15 regulation using a mouse skeletal muscle cell line, C2C12 cells. We found that the mRNA expression of IL-15, interleukin-2 receptor subunit beta (IL-2RB; CD122) and interleukin-2 receptor subunit gamma (IL-2RG; CD132) increased, but that IL-15RA exhibited different kinetics as differentiation progressed. We also found that IL-15, mainly present in the cytosol, pre-assembled with IL-15RA in the cytosol and fused to the plasma membrane. Moreover, IL-15RA increased IL-15 protein levels. Our findings suggest that genes involved in the IL-15 signalling complex are enhanced with the differentiation of myotubes and that IL-15RA regulates the protein kinetics of IL-15 signalling in skeletal muscle.
摘要：
这项研究的核心问题是什么？在成肌细胞分化为肌管的过程中，白细胞介素（IL）-15及其受体的动力学如何改变，以及IL-15是如何调节的？主要发现及其重要性是什么？在骨骼肌分化过程中，IL-15和白介素2受体亚基β和γ的mRNA水平增加，而白细胞介素-15受体亚基α（IL-15RA）表现出不同的动力学。IL-15RA在蛋白质水平上调节IL-15的定位和表达。
白细胞介素-15(IL-15)是在运动过程中在骨骼肌中产生的白细胞介素-2(IL-2)家族中的肌因子。IL-15的功能作用涉及骨骼肌的肌肉再生和代谢调节。有报道表明白介素-15受体亚单位α(IL-15RA)通过调节IL-15在免疫细胞中的定位而起作用。然而,IL-15及其受体的动力学，它调节骨骼肌分化中的IL-15通路，尚未澄清。在这项研究中,我们使用小鼠骨骼肌细胞系研究了IL-15调节的机制，C2C12细胞。我们发现IL-15、白细胞介素-2受体亚基β(IL-2RB;CD122)和白细胞介素-2受体亚基γ(IL-2RG;CD132)的mRNA表达增加,但随着分化的进展，IL-15RA表现出不同的动力学。我们还发现IL-15主要存在于细胞质中，在细胞质中与IL-15RA预组装并与质膜融合。此外，IL-15RA增加IL-15蛋白水平。我们的发现表明，参与IL-15信号传导复合物的基因随着肌管的分化而增强，并且IL-15RA调节骨骼肌中IL-15信号传导的蛋白质动力学。
白细胞介素-15(IL-15)是在运动过程中在骨骼肌中产生的白细胞介素-2(IL-2)家族中的肌因子。IL-15的功能作用涉及骨骼肌的肌肉再生和代谢调节。有报道表明白介素-15受体亚单位α(IL-15RA)通过调节IL-15在免疫细胞中的定位而起作用。然而,IL-15及其受体的动力学，它调节骨骼肌分化中的IL-15通路，尚未澄清。在这项研究中,我们使用小鼠骨骼肌细胞系研究了IL-15调节的机制，C2C12细胞。我们发现IL-15、白细胞介素-2受体亚基β(IL-2RB;CD122)和白细胞介素-2受体亚基γ(IL-2RG;CD132)的mRNA表达增加,但随着分化的进展，IL-15RA表现出不同的动力学。我们还发现IL-15主要存在于细胞质中，在细胞质中与IL-15RA预组装并与质膜融合。此外，IL-15RA增加IL-15蛋白水平。我们的发现表明，参与IL-15信号传导复合物的基因随着肌管的分化而增强，并且IL-15RA调节骨骼肌中IL-15信号传导的蛋白质动力学。
