TY - JOUR
T1 - Gene expression profiling in the early phases of DMD: a constant
molecular signature characterizes DMD muscle from early postnatal life throughout disease progression
AU - Pescatori, Mario
AU - Broccolini, Aldobrando
AU - Minetti, Carlo
AU - Bertini, Enrico
AU - Bruno, Claudio
AU - D'Amico, Adele
AU - Bernardini, Camilla
AU - Mirabella, Massimiliano
AU - Silvestri, Gabriella
AU - Giglio, Vincenzo
AU - Modoni, Anna
AU - Pedemonte, Marina
AU - Tasca, Giorgio
AU - Galluzzi, Giuliana
AU - Mercuri, Eugenio Maria
AU - Tonali, Pietro A.
AU - Ricci, Enzo
PY - 2007
Y1 - 2007
N2 - Genome-wide gene expression profiling of skeletal muscle from Duchenne muscular dystrophy (DMD) patients has been used to describe muscle tissue alterations in DMD children older than 5 years. By studying the expression profile of 19 patients younger than 2 years, we describe with high resolution the gene expression signature that characterizes DMD muscle during the initial or "presymptomatic" phase of the disease. We show that in the first 2 years of the disease, DMD muscle is already set to express a distinctive gene expression pattern considerably different from the one expressed by normal, age-matched muscle. This "dystrophic" molecular signature is characterized by a coordinate induction of genes involved in the inflammatory response, extracellular matrix (ECM) remodeling and muscle regeneration, and the reduced transcription of those involved in energy metabolism. Despite the lower degree of muscle dysfunction experienced, our younger patients showed abnormal expression of most of the genes reported as differentially expressed in more advanced stages of the disease. By analyzing our patients as a time series, we provide evidence that some genes, including members of three pathways involved in morphogenetic signaling-Wnt, Notch, and BMP-are progressively induced or repressed in the natural history of DMD.
AB - Genome-wide gene expression profiling of skeletal muscle from Duchenne muscular dystrophy (DMD) patients has been used to describe muscle tissue alterations in DMD children older than 5 years. By studying the expression profile of 19 patients younger than 2 years, we describe with high resolution the gene expression signature that characterizes DMD muscle during the initial or "presymptomatic" phase of the disease. We show that in the first 2 years of the disease, DMD muscle is already set to express a distinctive gene expression pattern considerably different from the one expressed by normal, age-matched muscle. This "dystrophic" molecular signature is characterized by a coordinate induction of genes involved in the inflammatory response, extracellular matrix (ECM) remodeling and muscle regeneration, and the reduced transcription of those involved in energy metabolism. Despite the lower degree of muscle dysfunction experienced, our younger patients showed abnormal expression of most of the genes reported as differentially expressed in more advanced stages of the disease. By analyzing our patients as a time series, we provide evidence that some genes, including members of three pathways involved in morphogenetic signaling-Wnt, Notch, and BMP-are progressively induced or repressed in the natural history of DMD.
KW - DMD
KW - microarrays
KW - DMD
KW - microarrays
UR - http://hdl.handle.net/10807/166581
U2 - 10.1096/fj.06-7285com
DO - 10.1096/fj.06-7285com
M3 - Article
SN - 0892-6638
SP - 1210
EP - 1226
JO - THE FASEB JOURNAL
JF - THE FASEB JOURNAL
ER -