Interleukin-6 affects pacsin3, ephrinA4 expression and cytoskeletal proteins in differentiating primary skeletal myoblasts through transcriptional and post-transcriptional mechanisms
Autor: | Tomasz Domoradzki, Marta Milewska, Małgorzata Gajewska, Maciej Błaszczyk, Alicja Majewska, Katarzyna Grzelkowska-Kowalczyk, Magdalena Hulanicka |
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Rok vydání: | 2019 |
Předmět: |
Histology
Cytoskeleton organization Transcription Genetic Myoblasts Skeletal Pathology and Forensic Medicine Proinflammatory cytokine Myokine medicine Myocyte Animals Insulin-Like Growth Factor I RNA Processing Post-Transcriptional Interleukin 6 Cytoskeleton Adaptor Proteins Signal Transducing biology Chemistry Interleukin-6 Skeletal muscle Cell Differentiation Cell Biology Ephrin-A4 Recombinant Proteins Cell biology Rats Cytoskeletal Proteins Disease Models Animal MicroRNAs medicine.anatomical_structure biology.protein Desmin |
Zdroj: | Cell and tissue research. 380(1) |
ISSN: | 1432-0878 |
Popis: | 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. |
Databáze: | OpenAIRE |
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