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Label‐free mass spectrometric analysis of the mdx‐4cv diaphragm identifies the matricellular protein periostin as a potential factor involved in dystrophinopathy‐related fibrosis
Author(s) -
Holland Ashling,
Dowling Paul,
Meleady Paula,
Henry Michael,
Zweyer Margit,
Mundegar Rustam R.,
Swandulla Dieter,
Ohlendieck Kay
Publication year - 2015
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201400471
Subject(s) - periostin , matricellular protein , plectin , mdx mouse , duchenne muscular dystrophy , muscular dystrophy , dystrophin , biology , utrophin , microbiology and biotechnology , pathology , fibrosis , decorin , desmin , dysferlin , extracellular matrix , chemistry , vimentin , immunology , medicine , cytoskeleton , intermediate filament , biochemistry , genetics , immunohistochemistry , proteoglycan , cell
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.