Parallel protein and transcript profiles of FSHD patient muscles correlate to the D4Z4 arrangement and reveal a common impairment of slow to fast fibre differentiation and a general deregulation of MyoD-dependent genes
Articolo
Data di Pubblicazione:
2006
Citazione:
Parallel protein and transcript profiles of FSHD patient muscles correlate to the D4Z4 arrangement and reveal a common impairment of slow to fast fibre differentiation and a general deregulation of MyoD-dependent genes / B. Celegato, D. Capitanio, M. Pescatori, C. Romualdi, B. Pacchioni, S. Cagnin, A. Viganò, L. Colantoni, S. Begum, E. Ricci, R. Wait, G. Lanfranchi, C. Gelfi, D. Capitanio. - In: PROTEOMICS. - ISSN 1615-9853. - 6:19(2006 Oct), pp. 5303-5321.
Abstract:
Here, we present the first study of a human neuromuscular disorder at transcriptional and proteomic level. Autosomal dominant facio-scapulo-humeral muscular dystrophy (FSHD) is caused by a deletion of an integral number of 3.3-kb KpnI repeats inside the telomeric region D4Z4 at the 4q35 locus. We combined a muscle-specific cDNA microarray platform with a proteomic investigation to analyse muscle biopsies of patients carrying a variable number of KpnI repeats.
Unsupervised cluster analysis divides patients into three classes, according to their KpnI repeat number. Expression data reveal a transition from fast-glycolytic to slow-oxidative phenotype in FSHD muscle, which is accompanied by a deficit of proteins involved in response to oxidative
stress. Besides, FSHD individuals show a disruption in the MyoD-dependent gene network
suggesting a coregulation at transcriptional level during myogenesis. We also discuss the hypothesis that D4Z4 contraction may affect in trans the expression of a set of genes involved in myogenesis, as well as in the regeneration pathway of satellite cells in adult tissue. Muscular wasting could result from the inability of satellite cells to successfully differentiate into mature fibres and from the accumulation of structural damages caused by a reactive oxygen species (ROS) imbalance induced by an increased oxidative metabolism in fibres.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
B. Celegato, D. Capitanio, M. Pescatori, C. Romualdi, B. Pacchioni, S. Cagnin, A. Viganò, L. Colantoni, S. Begum, E. Ricci, R. Wait, G. Lanfranchi, C. Gelfi, D. Capitanio
Link alla scheda completa:
Link al Full Text: