Abstract
Skeletal myofibers are injured due to mechanical stresses experienced during physical activity, or due to myofiber fragility caused by genetic diseases. The injured myofiber needs to be repaired or regenerated to restore the loss in muscle tissue function. Myofiber repair and regeneration requires coordinated action of various intercellular signaling factors—including proteins, inflammatory cytokines, miRNAs, and membrane lipids. It is increasingly being recognized release and transmission of these signaling factors involves extracellular vesicle (EV) released by myofibers and other cells in the injured muscle. Intercellular signaling by these EVs alters the phenotype of their target cells either by directly delivering the functional proteins and lipids or by modifying longer-term gene expression. These changes in the target cells activate downstream pathways involved in tissue homeostasis and repair. The EVs are heterogeneous with regards to their size, composition, cargo, location, as well as time-course of genesis and release. These differences impact on the subsequent repair and regeneration of injured skeletal muscles. This review focuses on how intracellular vesicle production, cargo packaging, and secretion by injured muscle, modulates specific reparative, and regenerative processes. Insights into the formation of these vesicles and their signaling properties offer new understandings of the orchestrated response necessary for optimal muscle repair and regeneration.
Highlights
Skeletal muscle comprises over a third of the total human body mass, making it one of our largest organ systems
This exemplifies cell-stress specific vesicle cargo production and packaging. Supporting this feature of mdx extracellular vesicle (EV), dystrophindeficient cardiomyocytes produce smaller EVs than healthy cardiomyocytes, but these vesicles have the unique capacity to protect neighboring cardiomyocytes from cell death following their uptake (Gartz et al, 2018). It has become increasingly clear from the mounting body of evidence in skeletal muscle injury, that EV secretion and extracellular signaling occurs along the continuum of muscle repair and regeneration
The studies discussed above suggest the existence of an injury-responsive production of EVs packaged with proteins, RNAs, and lipids to facilitate repair and regeneration
Summary
Skeletal muscle comprises over a third of the total human body mass, making it one of our largest organ systems. Responses triggered by damaged, repaired, regenerating, and degenerating myofibers, facilitate the intracellular signaling following membrane injury that supports healthy regeneration and growth of the injured muscle.
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