Characterization and Functional Analysis of Extracellular Vesicles and Muscle-Abundant miRNAs miR-1, miR-133a, and miR-206 in C2C12 Myocytes and mdx MiceReportar como inadecuado




Characterization and Functional Analysis of Extracellular Vesicles and Muscle-Abundant miRNAs miR-1, miR-133a, and miR-206 in C2C12 Myocytes and mdx Mice - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Duchenne muscular dystrophy DMD is a progressive neuromuscular disorder. Here, we show that the CD63 antigen, which is located on the surface of extracellular vesicles EVs, is associated with increased levels of muscle-abundant miRNAs, namely myomiRs miR-1, miR-133a, and miR-206, in the sera of DMD patients and mdx mice. Furthermore, the release of EVs from the murine myoblast C2C12 cell line was found to be modulated by intracellular ceramide levels in a Ca2+-dependent manner. Next, to investigate the effects of EVs on cell survival, C2C12 myoblasts and myotubes were cultured with EVs from the sera of mdx mice or C2C12 cells overexpressing myomiRs in presence of cellular stresses. Both the exposure of C2C12 myoblasts and myotubes to EVs from the serum of mdx mice, and the overexpression of miR-133a in C2C12 cells in presence of cellular stress resulted in a significant decrease in cell death. Finally, to assess whether miRNAs regulate skeletal muscle regeneration in vivo, we intraperitoneally injected GW4869 an inhibitor of exosome secretion into mdx mice for 5 and 10 days. Levels of miRNAs and creatine kinase in the serum of GW4869-treated mdx mice were significantly downregulated compared with those of controls. The tibialis anterior muscles of the GW4869-treated mdx mice showed a robust decrease in Evans blue dye uptake. Collectively, these results indicate that EVs and myomiRs might protect the skeletal muscle of mdx mice from degeneration.



Autor: Yasunari Matsuzaka, Jun Tanihata, Hirofumi Komaki, Akihiko Ishiyama, Yasushi Oya, Urs Rüegg, Shin-ichi Takeda, Kazuo Hashido

Fuente: http://plos.srce.hr/



DESCARGAR PDF




Documentos relacionados