Figure 2.

Proposed mechanisms of action of MMP-9 in DMD. Lack of dystrophin leads to destabilization of DGC, increased susceptibility to contraction-induced injury, and finally degeneration/regeneration of myofibers. Cycles of fiber degeneration and regeneration augment inflammatory response with concomitant activation of proinflammatory transcription factors NF-κB and AP-1. NF-κB, and AP-1 augments the gene expression of MMP-9. Increased production of MMP-9 also induces NF-κB and AP-1 activity potentially through proteolytic activation of various latent cytokines. Persistent presence of high levels of MMP-9 causes fiber necrosis, inflammation, and fibrosis and interferes with regeneration of damaged myofibers leading to myopathy. AP-1, activator protein 1; DGC, dystrophin-associated glycoprotein complex; DMD, Duchenne muscular dystrophy; MMP-9, matrix metalloproteinase-9; NF-κB, nuclear factor-kappa B.