Understanding the process of fibrosis in duchenne muscular dystrophy

Fibrosis is the aberrant deposition of extracellular matrix (ECM) components during tissue healing leading to loss of its architecture and function. Fibrotic diseases are often associated with chronic pathologies and occur in a large variety of vital organs and tissues, including skeletal muscle. In human muscle, fibrosis is most readily associated with the severe muscle wasting disorder Duchenne muscular dystrophy (DMD), caused by loss of dystrophin gene function. In DMD, skeletal muscle degenerates and is infiltrated by inflammatory cells and the functions of the muscle stem cells (satellite cells) become impeded and fibrogenic cells hyperproliferate and are overactivated, leading to the substitution of skeletal muscle with nonfunctional fibrotic tissue. Here, we review new developments in our understanding of the mechanisms leading to fibrosis in DMD and several recent advances towards reverting it, as potential treatments to attenuate disease progression.The authors thank C. Mann and the members of the Cell Biology Group for their helpful discussions and acknowledge funding from MINECO-Spain (SAF2012-38547, FIS-PS09/01267, FIS-PI13/025, and PLE2009-0124), AFM, E-Rare, Fundació MaratóTV3, Duchenne PP-NL, MDA, and EU-FP7 (Myoage, Optistem, and Endostem). Yacine Kharraz and Patrizia Pessina were supported by postdoctoral fellowships from AF