Fibrosis is the end result of a cascade of events that begins with tissue injury and inflammation and ends in permanent scar formation. When tissue is damaged, profibrotic cytokines, such as transforming growth factor beta, are released by the infiltrating inflammatory cells. These cytokines signal the fibroblasts to migrate into the affected region and to begin producing and remodeling the extracellular matrix. The stromal fibroblasts then begin producing cytokines, growth factors, and proteases that further trigger and uphold the inflammatory/profibrotic conditions. While fibroblasts are fundamental for maintaining tissue homeostasis and regulating normal wound repair, they also serve as a crucial intermediate in the formation of chronic fibrotic diseases. During conditions of chronic or extensive muscle damage, persistent inflammation, prolonged fibroblastic activation, and attenuated reparative capacity of the satellite cells ultimately lead to excessive accumulation of extracellular matrix components. This inhibits myogenic repair and leads to the replacement of muscle with fibrotic/scar tissue.
While nutritional, exertional, and toxic myopathies can result in extensive regions of muscle damage, repair is often extremely effective, and thus fibrosis is minimal to absent. In contrast, the reparative process is often ineffective following damage due to ischemia, likely due to the subsequent death of the satellite cells and endomysial cells. For this reason, extensive regions of fibrosis are often a dominant feature.
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