Adult healthy skeletal muscle has a powerful capacity to completely regenerate after an injury. On the opposite, muscular dystrophies (MDs) are devastating diseases where the regenerative capacities are overwhelmed and the muscle fibers are progressively replaced by fibrosis, leading to muscle loss of function and, finally to death, due to respiratory and cardiac failures. Since muscle stem cells are key factors in skeletal muscle regeneration, studies have mainly focused on the properties of these cells, as well as on their regulation by the neighboring cells. Despite the fact that excessive deposition of extracellular matrix (ECM) is the main cause of the loss of muscle function in MDs, investigation of ECM roles in muscle homeostasis remains scarce. The reason is that fibrosis is envisaged as one of the final outcomes of the disease. However, recent investigations in other tissues showed that ECM is an active partner of cells, and which dynamics is necessary for tissue remodeling. The project aimed to define the molecular ECM determinants at work during degenerative myopathies. The approach was to compare regenerative ECM (from healthy muscle undergoing regeneration) and dystrophic ECM (from diseased muscle) through proteomic-based mass spectrometry methodologies after obtaining sk-ECM from various mouse models by exploiting decellularization methods. The comparison between healthy regenerating (remodeling sk-ECM) and dystrophic (fibrotic sk-ECM) muscles allowed the identification of new molecular regulations from the ECM to various cell types in the muscle, notably the fibroadipogenic precursor cells, which are responsible for fibrosis.
