Interleukin (IL)-6 is a proinflammatory cytokine released in injured and contracting skeletal muscles. In this study, we examined cellular expression of proteins associated with cytoskeleton organization and cell migration, chosen on the basis of microRNA profiling, in rat primary skeletal muscle cells (RSkMC) treated with IL-6 (1 ng/ml) for 11 days. MiRNA microarray analysis and qRT-PCR revealed increased expression of miR-154-3p and miR-338-3p in muscle cells treated with IL-6. Pacsin3 was downregulated post-transcriptionally by IL-6, but not by IGF-I. Ephrin4A protein was increased both in IL-6- and IGF-I-treated myocytes. IL-6, but not IGF-I, stimulated migratory ability of RSkMC, examined in wound healing assay. Alpha-actinin protein was slightly augmented in RSKMC treated with IL-6, similarly to IGF-I. IL-6, but not IGF-I, upregulated desmin in differentiating RSkMC. IL-6 supplementation caused accumulation of alpha-actinin and desmin in near-nuclear area of muscle cells, which was manifested by increased ratio: mean near-nuclear fluorescence/mean peripheral cytoplasm fluorescence of these proteins. We concluded that IL-6, a known proinflammatory cytokine and a physical activity-associated myokine, acting during differentiation of primary skeletal muscle cells, alters expression of nonmuscle-specific miRNAs. This cytokine causes differential effects on pacsin-3 and ephrinA4, through post-transcriptional inhibition and stimulation, respectively. IL-6-exerted modifications of cytoskeletal proteins in muscle cells include both transcriptional (desmin and dynein heavy chain 5) and post-transcriptional activation (alpha-actinin). Moreover, IL-6 augments near-nuclear distribution of cytoskeletal proteins, alpha-actinin and desmin and promotes migration of myocytes. Such effects suggest that IL-6 plays a role during skeletal muscle regeneration, acting through mechanisms independent of regulation of myogenic program.

中文翻译：

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Interleukin-6 通过转录和转录后机制影响 pacsin3、ephrinA4 表达和细胞骨架蛋白在分化原代骨骼肌成肌细胞中的作用

白细胞介素 (IL)-6 是一种在受伤和收缩的骨骼肌中释放的促炎细胞因子。在这项研究中，我们检查了与细胞骨架组织和细胞迁移相关的蛋白质的细胞表达，这些蛋白质是根据 microRNA 分析选择的，在用 IL-6 (1 ng/ml) 处理 11 天的大鼠原代骨骼肌细胞 (RSkMC) 中。miRNA 微阵列分析和 qRT-PCR 显示，用 IL-6 处理的肌肉细胞中 miR-154-3p 和 miR-338-3p 的表达增加。Pacsin3 在转录后被 IL-6 下调，但不被 IGF-I 下调。Ephrin4A 蛋白在 IL-6 和 IGF-I 处理的肌细胞中均增加。在伤口愈合试验中检测到 IL-6，而不是 IGF-I，刺激了 RSkMC 的迁移能力。与 IGF-I 类似，在用 IL-6 处理的 RSKMC 中，α-辅肌动蛋白略有增加。IL-6，但不是 IGF-I，在区分 RSkMC 中上调结蛋白。IL-6 补充导致 α-辅肌动蛋白和结蛋白在肌肉细胞的近核区域积累，这表现为这些蛋白质的平均近核荧光/平均外周细胞质荧光的比率增加。我们得出结论，IL-6，一种已知的促炎细胞因子和一种与身体活动相关的肌因子，在初级骨骼肌细胞的分化过程中起作用，改变了非肌肉特异性 miRNA 的表达。这种细胞因子分别通过转录后抑制和刺激对 pacsin-3 和 ephrinA4 产生不同的影响。肌肉细胞中细胞骨架蛋白的 IL-6 修饰包括转录（结蛋白和动力蛋白重链 5）和转录后激活（α-辅肌动蛋白）。而且，IL-6 增强细胞骨架蛋白、α-辅肌动蛋白和结蛋白的近核分布，并促进肌细胞的迁移。这种效应表明 IL-6 在骨骼肌再生过程中发挥作用，通过独立于生肌程序调节的机制发挥作用。