Abnormal repair of skeletal muscle and development of fibrosis
The repair process of damaged tissue involves the coordinated activity of several cell types in response to local and systemic signals. Following acute tissue injury, infiltrating inflammatory cells and resident stem cells coordinate their activities to restore tissue homeostasis. However, during chronic tissue damage, such as muscular dystrophy, inflammatory cell infiltration and fibroblast activation persist, and the repair capacity of stem cells (satellite cells) is reduced. Abnormal dystrophic muscle repair and its terminal stage, fibrosis, represent the final common pathway of virtually all chronic neurodegenerative muscle diseases. As our understanding of the pathogenesis of myofibrosis has increased, it has become clear that muscle provides a useful model for the regulation of tissue repair by the local microenvironment and the interaction between muscle-specific stem cells, inflammatory cells, fibroblasts, and extracellular matrix components of the mammalian wound healing response. This article outlines new discoveries of the mechanisms underlying normal and abnormal muscle tissue repair.
Mann, CJ, Perdiguero, E., Kharraz, Y. etal. Abnormal skeletal muscle repair and the development of fibrosis. Skeletal Muscle 1, 21 (2011). https://doi.org/10.1186/2044-5040-1-21
Commentary
According to the description in this study, fibrosis is the end result of a complex series of events following tissue damage and inflammation. Defects in this one sequence can lead to excessive and persistent ECM deposition, replacing normal tissue with scar tissue and causing tissue dysfunction.
And dysregulated muscle repair with persistent fibrosis plays a prominent role in the clinical decline and reduced life expectancy associated with severe muscular dystrophy, especially in DMD. Thus, when fibrous tissue is repaired, dystrophic muscle turns in the direction of regeneration and if muscle integrity is maintained. The health of patients with muscular dystrophy may improve.
The obstacle of persistent fibrosis is that interventions aimed at restoring or replacing the dystrophin gene and stopping or reducing DMD fibrosis can reduce disease progression and are important for patients who cannot be treated in other ways.
This makes macrophages important for regulating tissue homeostasis and promoting aberrant healing, making them a key mediator of pathological skeletal remodeling in diseases such as IIM and dystrophy. Surfacing. Despite this role, macrophages in skeletal muscle have not been well characterized from a molecular perspective.
