Abstract

Matrix metalloproteinases (MMPs) have been implicated in the progression of muscular dystrophy, and recent studies have reported the role of MMP-10 in skeletal muscle pathology of young dystrophic mice. Nevertheless, its involvement in dystrophin-deficient hearts remains unexplored. Here, we aimed to investigate the involvement of MMP-10 in the progression of severe muscular dystrophy and to characterize MMP-10 loss in skeletal and cardiac muscles of aged dystrophic mice. We examined the histopathological effect of MMP-10 ablation in aged mdx mice, both in the hind limb muscles and heart tissues. We found that MMP-10 loss compromises survival rates of aged mdx mice, with skeletal and cardiac muscles developing a chronic inflammatory response. Our findings indicate that MMP-10 is implicated in severe muscular dystrophy progression, thus identifying a new area of research that could lead to future therapies for dystrophic muscles.

Highlights

  • Duchenne muscular dystrophy (DMD) is the most devastating X-linked muscular disorder, affecting approximately 1 in 3500 newborn males [1]

  • In order to evaluate the implications of Matrix metalloproteinases (MMPs)-10 in serious muscular dystrophy, mdx mice lacking MMP-10 were left to age

  • By using a mouse IgG-Cy3 antibody, we verified that the dystrophic condition significantly increased muscle necrosis, as monitored by intracellular fiber staining for IgG (Figure 1E,F), with loss of MMP-10 further deteriorating the dystrophic phenotype

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Summary

Introduction

Duchenne muscular dystrophy (DMD) is the most devastating X-linked muscular disorder, affecting approximately 1 in 3500 newborn males [1]. Mutations in the dystrophin gene result in a complete loss of the dystrophin protein or shorter or partially functional dystrophin. Dystrophin links the myofiber cytoskeleton to the extracellular matrix (ECM). Dystrophic muscles are more susceptible to muscular mechanical injury and sarcolemma damage, with myofibers undergoing continuous cycles of injury/repair. Under this chronic scenario, damage overcomes the regenerative potential of the muscle, contributing to progressive muscle wasting [1]. DMD patients suffer serious heart complications, which are responsible for premature death [2]

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