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首页> 外文期刊>Cell and Tissue Research >Interleukin-6 affects pacsin3, ephrinA4 expression and cytoskeletal proteins in differentiating primary skeletal myoblasts through transcriptional and post-transcriptional mechanisms
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Interleukin-6 affects pacsin3, ephrinA4 expression and cytoskeletal proteins in differentiating primary skeletal myoblasts through transcriptional and post-transcriptional mechanisms

机译：白细胞介素-6通过转录和转录后机制对分化初级骨骼肌进行影响，影响PACSIN3，Ephrina4表达和细胞骨架蛋白

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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.
机译：白细胞介素（IL）-6是在受伤和收缩骨骼肌中释放的促炎细胞因子。在这项研究中，我们检查了在用IL-6（1ng / ml）处理的大鼠初级骨骼肌细胞（RSKMC）的基础上选择了与细胞骨架组织和细胞迁移相关的蛋白质的细胞表达。 miRNA微阵列分析和QRT-PCR揭示了用IL-6处理的miR-154-3p和miR-338-3p表达的增加。 Pacsin3被IL-6转录后下调，但不是通过IGF-I。 Iphrin4a蛋白在IL-6-和IGF-I-处理的肌细胞中增加。 IL-6，但不是IGF-I，刺激RSKMC的迁移能力，在伤口愈合测定中检查。与IGF-I类似于IAL-6处理的RSKMC中，α-肌肽蛋白略微增加。 IL-6，但不是IGF-I，在差异化RSKMC时上调的亡灵。 IL-6补充导致肌肉细胞近核面积α-猕猴蛋白和去霉素的积累，其含量增加，这些蛋白的平均近核荧光/平均外周细胞质荧光。我们得出结论，IL-6，已知的促炎细胞因子和身体活性相关的肌管，在初级骨骼肌细胞的分化期间作用，改变了非用法特异性miRNA的表达。该细胞因子通过分别转录后抑制和刺激引起对普氏蛋白酶-3和Ephrina4的差异影响。 IL-6施加的肌肉细胞中细胞骨骼蛋白的修饰包括转录（Desmin和Dynin重链5）和转录后的激活（α-挥发型）。此外，IL-6增强了细胞骨骼蛋白的近核分布，α-挥发素蛋白和脱霉素，促进肌细胞的迁移。这些效果表明IL-6在骨骼肌再生期间发挥作用，通过独立于肌原遗传计划调节的机制作用。

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