Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/124527
Title: Gene expression profiling identifies molecular pathways associated with collagen VI deficiency and provides novel therapeutic targets
Author: Paco Mercader, Sonia
Kalko, Susana
Jou, Cristina
Rodríguez, María Angeles
Corbera, Joan
Muntoni, Francesco
Feng, Lucy
Rivas, Eloy
Torner Rubies, Ferran
Gualandi, Francesca
Gomez-Foix, Anna M.
Ferrer, Anna
Ortez, Carlos Ignacio
Nascimento, Andrés
Colomer Oferil, Jaume
Jiménez Mallebrera, Cecilia
Keywords: Expressió gènica
Genètica molecular humana
Distròfia muscular
Gene expression
Human molecular genetics
Muscular dystrophy
Issue Date: 11-Oct-2013
Publisher: Public Library of Science (PLoS)
Abstract: Ullrich congenital muscular dystrophy (UCMD), caused by collagen VI deficiency, is a common congenital muscular dystrophy. At present, the role of collagen VI in muscle and the mechanism of disease are not fully understood. To address this we have applied microarrays to analyse the transcriptome of UCMD muscle and compare it to healthy muscle and other muscular dystrophies. We identified 389 genes which are differentially regulated in UCMD relative to controls. In addition, there were 718 genes differentially expressed between UCMD and dystrophin deficient muscle. In contrast, only 29 genes were altered relative to other congenital muscular dystrophies. Changes in gene expression were confirmed by real-time PCR. The set of regulated genes was analysed by Gene Ontology, KEGG pathways and Ingenuity Pathway analysis to reveal the molecular functions and gene networks associated with collagen VI defects. The most significantly regulated pathways were those involved in muscle regeneration, extracellular matrix remodelling and inflammation. We characterised the immune response in UCMD biopsies as being mainly mediated via M2 macrophages and the complement pathway indicating that anti-inflammatory treatment may be beneficial to UCMD as for other dystrophies. We studied the immunolocalisation of ECM components and found that biglycan, a collagen VI interacting proteoglycan, was reduced in the basal lamina of UCMD patients. We propose that biglycan reduction is secondary to collagen VI loss and that it may be contributing towards UCMD pathophysiology. Consequently, strategies aimed at over-expressing biglycan and restore the link between the muscle cell surface and the extracellular matrix should be considered.
Note: Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0077430
It is part of: PLoS One, 2013, vol. 8, num. 10, p. 1-15
URI: http://hdl.handle.net/2445/124527
Related resource: https://doi.org/10.1371/journal.pone.0077430
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)
Articles publicats en revistes (Biomedicina)

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