Label‐free mass spectrometric analysis of the mdx‐4cv diaphragm identifies the matricellular protein periostin as a potential factor involved in dystrophinopathy‐related fibrosis. Issue 13 (1st April 2015)

• Record Type: Journal Article
• Authors: Holland, Ashling; Dowling, Paul; Meleady, Paula; Henry, Michael; Zweyer, Margit; Mundegar, Rustam R.; Swandulla, Dieter; Ohlendieck, Kay
• Is Part Of: Proteomics. Volume 15:Issue 13(2015:Jul.)
• Page Start: 2318
• Page End: 2331
• Publication Date: 2015-04-01
• Subjects: Proteins -- Separation -- Periodicals; Bioinformatics -- Periodicals; Proteomics -- Periodicals; Genomes -- Periodicals; Molecular genetics -- Periodicals; 572.605
• DOI: 10.1002/pmic.201400471
• Languages: English
• ISSNs: 1615-9853

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 <italic>mdx‐4cv</italic> mouse. This animal model of progressive muscle wasting exhibits less dystrophin‐positive revertant fibers than the conventional <italic>mdx</italic> mouse, making it ideal for the future monitoring of experimental therapies. The pathoproteomic signature of the <italic>mdx‐4cv</italic> 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 <italic>mdx</italic> and <italic>mdx‐4cv</italic> mice, suggesting an involvement of this matricellular protein in dystrophinopathy‐related fibrosis.</p> </abstract>