Sequenced response of extracellular matrix deadhesion and fibrotic regulators after muscle damage is involved in protection against future injury in human skeletal muscle

Abstract

The purpose of this study was to test the hypothesis that remodeling of skeletal muscle extracellular matrix (ECM) is involved in protecting human muscle against injury. Biopsies were obtained from medial gastrocnemius muscles after a single bout of electrical stimulation (B) or a repeated bout (RB) 30 d later, or 30 d after a single stimulation bout (RBc). A muscle biopsy was collected from the control leg for comparison with the stimulated leg. Satellite cell content, tenascin C, and muscle regeneration were assessed by immunohistochemistry; real-time PCR was used to measure mRNA levels of collagens, laminins, heat-shock proteins (HSPs), inflammation, and related growth factors. The large responses of HSPs, CCL2, and tenascin C detected 48 h after a single bout were attenuated in the RB trial, indicative of protection against injury. Satellite cell content and 12 target genes, including IGF-1, were elevated 30 d after a single bout. Among those displaying the greatest difference vs. control muscle, ECM laminin-β1 and collagen types I and III were elevated ∼6- to 9-fold (P<0.001). The findings indicate that the sequenced events of load-induced early deadhesion and later strengthening of skeletal muscle ECM play a role in protecting human muscle against future injury.

Two maximal isometric contractions attenuate the magnitude of eccentric exercise-induced muscle damage

“…To explain possible mechanisms of the protective effect conferred by "eccentric contractions," McHugh (2003) categorized the potential adaptations as neural, mechanical, cellular, and others. Mackey et al (2011) have recently reported that the extracellular matrix is strengthened following 180 isometric contractions evoked by electrical stimulation, and that muscle damage in the subsequent bout that was performed 28 days later was attenuated. It is not known whether any changes in the extracellular matrix are produced by isometric contractions.…”

Electrical stimulation for neuromuscular testing and training: state-of-the art and unresolved issues

“…Acute effects Mackey et al (2011) recently showed that NMES-induced damage of the human medial gastrocnemius muscle results in de-adhesive, disassembly, and disorganization responses in the contractile connective tissue, followed by a delayed anabolic response leading to extracellular matrix remodelling. Besides these responses, the other mechanisms underlying NMES-induced muscle damage remain to be clarified.…”

Does an NSAID a day keep satellite cells at bay?

“…The highly organized arrangement of proteins making up the connective tissue network of skeletal muscle is capable, through mechanotransduction, of initiating signaling pathways in cells located in its environment (88) and undergoes extensive remodeling during regeneration and ageing (23,30). The adaptation of muscle connective tissue to exercise is a complex process and consists of an early phase of deadhesion and disassembly of the matrix, followed by a strong matrix anabolic phase that occurs late in the regeneration process (37). Interestingly, the delayed anabolic matrix activity was associated with a persistent elevation in the satellite cell content of the regenerating muscle 30 days after muscle damage was induced, compared with a biopsy collected from the control leg at the same time point (37), raising the possibility that cross talk between satellite cells and the muscle connective tissue matrix exists.…”

“…The adaptation of muscle connective tissue to exercise is a complex process and consists of an early phase of deadhesion and disassembly of the matrix, followed by a strong matrix anabolic phase that occurs late in the regeneration process (37). Interestingly, the delayed anabolic matrix activity was associated with a persistent elevation in the satellite cell content of the regenerating muscle 30 days after muscle damage was induced, compared with a biopsy collected from the control leg at the same time point (37), raising the possibility that cross talk between satellite cells and the muscle connective tissue matrix exists. Indeed it has been proposed that the fate of the satellite cell, in contact with the myofiber on one side and the basement membrane on the other side, is determined by the different receptors present on the two sides (see Fig.…”