Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Department of Anatomy, Biochemistry and Physiology, John A. Burns School of Medicine, Institute for Biogenesis Research, University of Hawaii, Honolulu, HI, USA.
Exp Physiol. 2022 Mar;107(3):222-232. doi: 10.1113/EP090205. Epub 2022 Feb 20.
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.
这项研究的核心问题是什么？白细胞介素（IL）-15 及其受体在成肌细胞分化为肌管的过程中如何发生动态变化，以及 IL-15 如何被调控？主要发现及其重要性是什么？在骨骼肌分化过程中，IL-15 和白细胞介素-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）则表现出不同的动力学。IL-15RA 调节 IL-15 在蛋白质水平上的定位和表达。
白细胞介素-15（IL-15）是 IL-2 家族中的一种肌肉因子，在运动时产生于骨骼肌中。IL-15 的功能作用涉及骨骼肌再生和代谢调节。有报道称，白细胞介素-15 受体亚基α（IL-15RA）通过调节免疫细胞中 IL-15 的定位来发挥作用。然而，调节骨骼肌分化中 IL-15 途径的 IL-15 和其受体的动态变化尚未阐明。在这项研究中，我们使用小鼠骨骼肌细胞系 C2C12 细胞研究了 IL-15 的调控机制。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 IL-15RA 的表达随分化的进行而呈现不同的动力学。我们还发现，IL-15 主要存在于细胞质中，与细胞质中的 IL-15RA 预组装并融合到质膜上。此外，IL-15RA 增加了 IL-15 蛋白水平。我们的研究结果表明，与肌管分化相关的 IL-15 信号复合物相关基因增强，并且 IL-15RA 调节骨骼肌中 IL-15 信号的蛋白动力学。
