G.P.21 Proteomic analysis of cultured skin fibroblasts from UCMD patients reveals the involvement of two new cellular pathways

• Published in: Neuromuscular disorders : NMD Vol. 22; no. 9; pp. 828 - 829
• Main Authors: Deconinck, N, Mussche, S, De Paepe, B, Gartioux, C, Allamand, V, Richard, P, Smet, J, Devreese, B, Coster, R. Van
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-10-2012
• Subjects: Indexing in process; Neurology
• ISSN: 0960-8966; 1873-2364
• DOI: 10.1016/j.nmd.2012.06.091

Abstract Ullrich congenital muscular dystrophy (UCMD) is a severe congenital dystrophy caused by collagen VI mutations and resulting in absent or aberrant collagen VI secretion in fibroblasts, the main collagen VI secreting cells. ColVI is a ubiquitous extracellular matrix (ECM) protein that forms a microfibrillar network in close association with the basement membrane in many tissues. ColVI was shown to interact with several ECM components. Although an increased apoptotic rate, a mitochondrial defect and an impairment of the autophagocytic flux have been described in myoblasts and muscle cells from ColVI-deficient mice, the molecular pathways that link ColVI to the basal membrane protein network (fibronectin, etc.) and the downstream intracellular mechanisms are not fully elucidated. We present the results of a proteomic comparison between cultured skin fibroblasts from four unrelated UCMD patients, all carrying the heterozygous de novo p.G284R mutation in the COL6A1 gene, and fibroblasts from controls. Some of the dysregulated proteins observed in the proteomic profiles were confirmed by western blot, qPCR analysis, and fibroblast immunohistochemical staining. A detailed description of the new protein networks will be presented. Our results point to the involvement of two major cellular pathways that have up to now not been described in UCMD fibroblasts, which besides their role in the muscle disease, display typical abnormalities in other tissues like skin and tendons. We propose new insights in the pathophysiology of this matrix disease.