MECHANISMS OF FIBROSIS IN MUSCULAR DYSTROPHIES

Fibrosis refers to the excessive accumulation of connective tissue within an organ. It is prominent in a variety of degenerative and inflammatory diseases, including Duchenne muscular dystrophy (DMD). DMD occurs due to a genetic defect in the gene encoding the dystrophin protein. The absence of dystrophin causes chronic cycles of degeneration and regeneration of the muscles fibers, which are responsible for the contractile ability of the muscles. With the progression of the disease, the regenerative ability of muscle becomes progressively impaired and fibrotic tissue accumulates leading to a severe reduction in muscle function. Although some pharmacological approaches are partially delaying the outcome of the disease, no definitive treatment for DMD is available at the moment. Therefore, there is much interest in identifying new therapeutic targets to counteract the progression of the disease and resolve fibrosis. By employing a combination of in vitro and in vivo approaches, our studies are exploring the cellular and molecular mechanisms responsible for stem cell dysfunction and accumulation of fibrotic tissue in dystrophic muscle in order to set up the basis for more effective and specific therapeutic approaches.