Collagens and Muscle Diseases: A Focus on Collagen VI

The extracellular matrix is a three-dimensional network providing the proper microenvironment for muscle development and function. Different types of collagens play critical roles in skeletal muscle homeostasis, as revealed by the fact that mutations in distinct collagen genes are linked to inherited muscle disorders, including some forms of myopathies and congenital muscular dystrophies. The following chapter discusses the current knowledge of collagens and their roles in muscle disorders, mostly focusing on collagen VI since it is the collagen type with the major known impact in muscle physiology and whose deficiency is causative for a distinctive group of muscle diseases. Collagen VI is a unique member of the collagen superfamily, displaying distinctive protein domains, supramolecular assembly, and tissue distribution. Moreover, it exerts a broad range of essential functions in the skeletal muscle, and mutations of its genes are linked to congenital muscular dystrophies and congenital myopathies. Mutant and knockout animal models for collagen VI and other collagen types provided a tremendous tool for the mechanistic understanding of human muscle diseases linked to collagens’ defects and, thus, for translational studies. Indeed, the increasing knowledge on the underlying pathomolecular mechanisms and the identification of suitable targets represent invaluable benefits for proper clinical diagnosis and for developing treatments and therapeutic opportunities to counteract the onset and progression of clinical symptoms of such severe and often life-threatening muscle pathologies.