Molecular pathogenesis of Duchenne muscular dystrophy-related fibrosis

Progressive myofibrosis plays a key role in Duchenne muscular dystrophy. The dystrophic loss of contractile cells triggers a relatively nonspecific restructuring of the surrounding mesenchyme. The increase in connective and fatty tissue leads to muscular weakness and is therefore of critical importance for the cellular pathogenesis of muscular dystrophy. The systematic biochemical analysis of fibrosis using comparative proteomics has identified a number of extracellular matrix proteins that are indirectly involved in muscular dystrophy. An increased concentration was established for collagen I, collagen IV, collagen VI, periostin, dermatopontin, fibronectin, biglycan, asporin, decorin, prolargin, mimecan and lumican. Based on these findings, the identified matrix proteins can now be characterized biochemically and their exact pathophysiological role in Duchenne muscular dystrophy determined.