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Mechanisms of Muscle Injury, Repair, and Regeneration
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TLDR
The process of muscle injury, repair and regeneration that occurs in muscular dystrophy is used as an example of chronic muscle injury to highlight similarities and differences between the injury and repair processes that occur in acutely and chronically injured muscle.Abstract:
Skeletal muscle continuously adapts to changes in its mechanical environment through modifications in gene expression and protein stability that affect its physiological function and mass. However, mechanical stresses commonly exceed the parameters that induce adaptations, producing instead acute injury. Furthermore, the relatively superficial location of many muscles in the body leaves them further vulnerable to acute injuries by exposure to extreme temperatures, contusions, lacerations or toxins. In this article, the molecular, cellular, and mechanical factors that underlie muscle injury and the capacity of muscle to repair and regenerate are presented. Evidence shows that muscle injuries that are caused by eccentric contractions result from direct mechanical damage to myofibrils. However, muscle pathology following other acute injuries is largely attributable to damage to the muscle cell membrane. Many feaures in the injury-repair-regeneration cascade relate to the unregulated influx of calcium through membrane lesions, including: (i) activation of proteases and hydrolases that contribute muscle damage, (ii) activation of enzymes that drive the production of mitogens and motogens for muscle and immune cells involved in injury and repair, and (iii) enabling protein-protein interactions that promote membrane repair. Evidence is also presented to show that the myogenic program that is activated by acute muscle injury and the inflammatory process that follows are highly coordinated, with myeloid cells playing a central role in modulating repair and regeneration. The early-invading, proinflammatory M1 macrophages remove debris caused by injury and express Th1 cytokines that play key roles in regulating the proliferation, migration, and differentiation of satellite cells. The subsequent invasion by anti-inflammatory, M2 macrophages promotes tissue repair and attenuates inflammation. Although this system provides an effective mechanism for muscle repair and regeneration following acute injury, it is dysregulated in chronic injuries. In this article, the process of muscle injury, repair and regeneration that occurs in muscular dystrophy is used as an example of chronic muscle injury, to highlight similarities and differences between the injury and repair processes that occur in acutely and chronically injured muscle.read more
Citations
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Progressive fatigue dynamic development of isolated natively musculus gastrocnemius medialis in alcoholic rats
Olexiy Melnychuk,Olexandr Motuziuk,Svitlana Shvayko,Svitlana Yu. Zay,Олексій Анатолійович Мельничук,Олександр Петрович Мотузюк,Світлана Євгеніївна Швайко,Світлана Зай +7 more
TL;DR: The results of research shows the absence of significant changes in isolated natively musculus gastrocnemius medialis development progressive fatigue in alcoholic rats, in comparison to intact animals.
Additional file 3: Figure S3. of Muscle-specific deletion of SOCS3 increases the early inflammatory response but does not affect regeneration after myotoxic injury
Kristy Swiderski,Savant S Thakur,Timur Naim,Jennifer Trieu,Annabel Chee,David Stapleton,René Koopman,Gordon S. Lynch +7 more
TL;DR: Loss of SOCS3 expression in mature muscle fibers increased the inflammatory response to myotoxic injury but did not impair muscle regeneration in either adult or old mice, suggesting reduced SOCS 3 expression in muscle fibers is unlikely to underlie impaired muscle regeneration.
Journal ArticleDOI
A Novel Homozygous Variant in DYSF Gene Is Associated with Autosomal Recessive Limb Girdle Muscular Dystrophy R2/2B
Patrizia Spadafora,Antonio Qualtieri,F Cavalcanti,G. Di Palma,Olivier Gallo,Selene De Benedittis,Annamaria Cerantonio,Luigi Citrigno +7 more
TL;DR: A new missense variant c.5033G>A in the exon 45 of DYSF gene related to Limb Girdle Muscular Dystrophy type R2/2B in a 57-year-old patient affected with LGMD from a consanguineous family of south Italy is reported, pointing at the NGS as powerful tool for identifying LGMD subtypes.
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