Label-free mass spectrometric analysis of the mdx-4cv diaphragm identifies the matricellular protein periostin as a potential factor involved in dystrophinopathy-related fibrosis.
Proteomic profiling plays a decisive role in the identification of novel biomarkers of muscular dystrophy and the elucidation of new pathobiochemical mechanisms that underlie progressive muscle wasting. Building on the findings of recent comparative analyses of tissue samples and body fluids from dystrophic animals and patients afflicted with Duchenne muscular dystrophy, we have used here label-free MS to study the severely dystrophic diaphragm from the not extensively characterized mdx-4cv mouse. This animal model of progressive muscle wasting exhibits less dystrophin-positive revertant fibers than the conventional mdx mouse, making it ideal for the future monitoring of experimental therapies. The pathoproteomic signature of the mdx-4cv diaphragm included a significant increase in the fibrosis marker collagen and related extracellular matrix proteins (asporin, decorin, dermatopontin, prolargin) and cytoskeletal proteins (desmin, filamin, obscurin, plectin, spectrin, tubulin, vimentin, vinculin), as well as decreases in proteins of ion homeostasis (parvalbumin) and the contractile apparatus (myosin-binding protein). Importantly, one of the most substantially increased proteins was identified as periostin, a matricellular component and apparent marker of fibrosis and tissue damage. Immunoblotting confirmed a considerable increase of periostin in the dystrophin-deficient diaphragm from both mdx and mdx-4cv mice, suggesting an involvement of this matricellular protein in dystrophinopathy-related fibrosis.
Department of Biology, Maynooth University, National University of Ireland, Maynooth, County Kildare, Ireland.
Ashling
A
Holland
Department of Biology, Maynooth University, National University of Ireland, Maynooth, County Kildare, Ireland.
Paul
P
Dowling
National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.
Paula
P
Meleady
National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.
Michael
M
Henry
Department of Physiology II, University of Bonn, Bonn, Germany.
Margit
M
Zweyer
Department of Physiology II, University of Bonn, Bonn, Germany.
Rustam R
RR
Mundegar
Department of Physiology II, University of Bonn, Bonn, Germany.
Dieter
D
Swandulla
Department of Biology, Maynooth University, National University of Ireland, Maynooth, County Kildare, Ireland.
Kay
K
Ohlendieck
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D019295:Computational Biology; D003964:Diaphragm / Q000378:metabolism*; D066298:In Vitro Techniques; D051379:Mice; D018101:Mice, Inbred mdx; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
D015815:Cell Adhesion Molecules; C082838:Postn protein, mouse
Animal proteomics; Collagen; Duchenne muscular dystrophy; Fibrosis; Matricellular protein; Periostin