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Title: Transcriptomic profiling of TK2 deficient human skeletal muscle suggests a role for the p53 signalling pathway and identifies growth and differentiation factor-15 as a potential novel biomarker for mitochondrial myopathies
Author: Kalko, Susana
Paco Mercader, Sonia
Jou, Cristina
Rodríguez, Maria Angels
Meznaric, Marija
Rogac, Mihael
Jekovec-Vrhovsek, Maja
Sciacco, Monica
Moggio, Maurizio
Fagiolari, Gigliola
De Paepe, Boel
De Meirleir, Linda
Ferrer, Isidro (Ferrer Abizanda)
Roig Quilis, Manuel
Munell Casadesús, Francina
Montoya, Julio
López-Gallardo, Ester
Ruiz-Pesini, Eduardo
Artuch Iriberri, Rafael
Montero Sánchez, Raquel
Torner Rubies, Ferran
Nascimento, Andrés
Ortez,Carlos Ignacio
Colomer, Jaume
Jiménez Mallebrera, Cecilia
Keywords: Expressió gènica
Microxips d'ADN
ADN mitocondrial
Malalties del sistema nerviós central
Gene expression
DNA microarrays
Mitochondrial DNA
Central nervous system diseases
Issue Date: 1-Feb-2014
Publisher: BioMed Central
Abstract: BACKGROUND: Mutations in the gene encoding thymidine kinase 2 (TK2) result in the myopathic form of mitochondrial DNA depletion syndrome which is a mitochondrial encephalomyopathy presenting in children. In order to unveil some of the mechanisms involved in this pathology and to identify potential biomarkers and therapeutic targets we have investigated the gene expression profile of human skeletal muscle deficient for TK2 using cDNA microarrays. RESULTS: We have analysed the whole transcriptome of skeletal muscle from patients with TK2 mutations and compared it to normal muscle and to muscle from patients with other mitochondrial myopathies. We have identified a set of over 700 genes which are differentially expressed in TK2 deficient muscle. Bioinformatics analysis reveals important changes in muscle metabolism, in particular, in glucose and glycogen utilisation, and activation of the starvation response which affects aminoacid and lipid metabolism. We have identified those transcriptional regulators which are likely to be responsible for the observed changes in gene expression. CONCLUSION: Our data point towards the tumor suppressor p53 as the regulator at the centre of a network of genes which are responsible for a coordinated response to TK2 mutations which involves inflammation, activation of muscle cell death by apoptosis and induction of growth and differentiation factor 15 (GDF-15) in muscle and serum. We propose that GDF-15 may represent a potential novel biomarker for mitochondrial dysfunction although further studies are required.
Note: Reproducció del document publicat a:
It is part of: Bmc Genomics, 2014, num. 15, p. 91
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ISSN: 1471-2164
Appears in Collections:Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)
Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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