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GIUSEPPE MORICI

Duchenne Muscular Dystrophy (DMD): Should it be Considered a Systemic Disease?

Abstract

Duchenne muscular dystrophy (DMD) is an X-linked muscle disease characterized by progressive skeletal muscle loss and development of respiratory failure due to involvement of respiratory muscles. Similar to human DMD, the mdx mouse model lacks dystrophin but is characterized by relatively mild muscle injury, allowing testing the effects of mild endurance exercise training on dystrophic skeletal muscle. We were interested to study the effects of exercise training on airway cells in trained mdx mice by applying the same protocol previously tested in Swiss mice. We found that mdx mice showed little airway inflammation associated with training, but developed increasing apoptosis of airway cells over time, irrespective of the trained or sedentary status. These findings suggested subclinical progressive exhaustion of protective mechanisms in airway epithelium of the mdx mouse, possibly involving chaperonin Hsp60. Moreover, a paucity of goblet cells was shown in the airways of mdx mice at all-time points of the study, independently of the sedentary or trained condition. We speculate that a disturbance of the Notch pathway, which has already been described in dystrophic skeletal muscles, might be involved in the almost absent secretory cell phenotype found in the airways of mdx mice. Overall, our findings suggest that dystrophin might affect other tissues beyond skeletal muscles, and exert physiologic effects, which at present are poorly defined, in non-muscular tissues.