Different molecular signatures in magnetic resonance imaging-staged facioscapulohumeral muscular dystrophy muscles

Giorgio Tasca, Mario Pescatori, Mauro Monforte, Massimiliano Mirabella, Elisabetta Iannaccone, Roberto Frusciante, Tiziana Cubeddu, Francesco Laschena, Pierfrancesco Ottaviani, Enzo Ricci

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Background: Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies and is characterized by a non-conventional genetic mechanism activated by pathogenic D4Z4 repeat contractions. By muscle Magnetic Resonance Imaging (MRI) we observed that T2-short tau inversion recovery (T2-STIR) sequences identify two different conditions in which each muscle can be found before the irreversible dystrophic alteration, marked as T1-weighted sequence hyperintensity, takes place. We studied these conditions in order to obtain further information on the molecular mechanisms involved in the selective wasting of single muscles or muscle groups in this disease. Methods: Histopathology, gene expression profiling and real time PCR were performed on biopsies from FSHD muscles with different MRI pattern (T1-weighted normal/T2-STIR normal and T1-weighted normal/T2-STIR hyperintense). Data were compared with those from inflammatory myopathies, dysferlinopathies and normal controls. In order to validate obtained results, two additional FSHD samples with different MRI pattern were analyzed. Results: Myopathic and inflammatory changes characterized T2-STIR hyperintense FSHD muscles, at variance with T2-STIR normal muscles. These two states could be easily distinguished from each other by their transcriptional profile. The comparison between T2-STIR hyperintense FSHD muscles and inflammatory myopathy muscles showed peculiar changes, although many alterations were shared among these conditions. Conclusions: At the single muscle level, different stages of the disease correspond to the two MRI patterns. T2-STIR hyperintense FSHD muscles are more similar to inflammatory myopathies than to T2-STIR normal FSHD muscles or other muscular dystrophies, and share with them upregulation of genes involved in innate and adaptive immunity. Our data suggest that selective inflammation, together with perturbation in biological processes such as neoangiogenesis, lipid metabolism and adipokine production, may contribute to the sequential bursts of muscle degeneration that involve individual muscles in an asynchronous manner in this disease.

Original languageEnglish
Article numbere38779
JournalPLoS One
Volume7
Issue number6
DOIs
Publication statusPublished - Jun 13 2012

Fingerprint

Facioscapulohumeral Muscular Dystrophy
muscular dystrophy
Magnetic resonance
magnetic resonance imaging
Muscle
Magnetic Resonance Imaging
Imaging techniques
Muscles
muscles
Recovery
Myositis
muscular diseases
Muscular Dystrophies
Sequence Inversion
Biological Phenomena
adipokines
Adipokines
Biopsy
Gene Expression Profiling
Adaptive Immunity

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Tasca, G., Pescatori, M., Monforte, M., Mirabella, M., Iannaccone, E., Frusciante, R., ... Ricci, E. (2012). Different molecular signatures in magnetic resonance imaging-staged facioscapulohumeral muscular dystrophy muscles. PLoS One, 7(6), [e38779]. https://doi.org/10.1371/journal.pone.0038779

Different molecular signatures in magnetic resonance imaging-staged facioscapulohumeral muscular dystrophy muscles. / Tasca, Giorgio; Pescatori, Mario; Monforte, Mauro; Mirabella, Massimiliano; Iannaccone, Elisabetta; Frusciante, Roberto; Cubeddu, Tiziana; Laschena, Francesco; Ottaviani, Pierfrancesco; Ricci, Enzo.

In: PLoS One, Vol. 7, No. 6, e38779, 13.06.2012.

Research output: Contribution to journalArticle

Tasca, G, Pescatori, M, Monforte, M, Mirabella, M, Iannaccone, E, Frusciante, R, Cubeddu, T, Laschena, F, Ottaviani, P & Ricci, E 2012, 'Different molecular signatures in magnetic resonance imaging-staged facioscapulohumeral muscular dystrophy muscles', PLoS One, vol. 7, no. 6, e38779. https://doi.org/10.1371/journal.pone.0038779
Tasca, Giorgio ; Pescatori, Mario ; Monforte, Mauro ; Mirabella, Massimiliano ; Iannaccone, Elisabetta ; Frusciante, Roberto ; Cubeddu, Tiziana ; Laschena, Francesco ; Ottaviani, Pierfrancesco ; Ricci, Enzo. / Different molecular signatures in magnetic resonance imaging-staged facioscapulohumeral muscular dystrophy muscles. In: PLoS One. 2012 ; Vol. 7, No. 6.
@article{11cec685f08c4d9884ec4ad387f36f46,
title = "Different molecular signatures in magnetic resonance imaging-staged facioscapulohumeral muscular dystrophy muscles",
abstract = "Background: Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies and is characterized by a non-conventional genetic mechanism activated by pathogenic D4Z4 repeat contractions. By muscle Magnetic Resonance Imaging (MRI) we observed that T2-short tau inversion recovery (T2-STIR) sequences identify two different conditions in which each muscle can be found before the irreversible dystrophic alteration, marked as T1-weighted sequence hyperintensity, takes place. We studied these conditions in order to obtain further information on the molecular mechanisms involved in the selective wasting of single muscles or muscle groups in this disease. Methods: Histopathology, gene expression profiling and real time PCR were performed on biopsies from FSHD muscles with different MRI pattern (T1-weighted normal/T2-STIR normal and T1-weighted normal/T2-STIR hyperintense). Data were compared with those from inflammatory myopathies, dysferlinopathies and normal controls. In order to validate obtained results, two additional FSHD samples with different MRI pattern were analyzed. Results: Myopathic and inflammatory changes characterized T2-STIR hyperintense FSHD muscles, at variance with T2-STIR normal muscles. These two states could be easily distinguished from each other by their transcriptional profile. The comparison between T2-STIR hyperintense FSHD muscles and inflammatory myopathy muscles showed peculiar changes, although many alterations were shared among these conditions. Conclusions: At the single muscle level, different stages of the disease correspond to the two MRI patterns. T2-STIR hyperintense FSHD muscles are more similar to inflammatory myopathies than to T2-STIR normal FSHD muscles or other muscular dystrophies, and share with them upregulation of genes involved in innate and adaptive immunity. Our data suggest that selective inflammation, together with perturbation in biological processes such as neoangiogenesis, lipid metabolism and adipokine production, may contribute to the sequential bursts of muscle degeneration that involve individual muscles in an asynchronous manner in this disease.",
author = "Giorgio Tasca and Mario Pescatori and Mauro Monforte and Massimiliano Mirabella and Elisabetta Iannaccone and Roberto Frusciante and Tiziana Cubeddu and Francesco Laschena and Pierfrancesco Ottaviani and Enzo Ricci",
year = "2012",
month = "6",
day = "13",
doi = "10.1371/journal.pone.0038779",
language = "English",
volume = "7",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - Different molecular signatures in magnetic resonance imaging-staged facioscapulohumeral muscular dystrophy muscles

AU - Tasca, Giorgio

AU - Pescatori, Mario

AU - Monforte, Mauro

AU - Mirabella, Massimiliano

AU - Iannaccone, Elisabetta

AU - Frusciante, Roberto

AU - Cubeddu, Tiziana

AU - Laschena, Francesco

AU - Ottaviani, Pierfrancesco

AU - Ricci, Enzo

PY - 2012/6/13

Y1 - 2012/6/13

N2 - Background: Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies and is characterized by a non-conventional genetic mechanism activated by pathogenic D4Z4 repeat contractions. By muscle Magnetic Resonance Imaging (MRI) we observed that T2-short tau inversion recovery (T2-STIR) sequences identify two different conditions in which each muscle can be found before the irreversible dystrophic alteration, marked as T1-weighted sequence hyperintensity, takes place. We studied these conditions in order to obtain further information on the molecular mechanisms involved in the selective wasting of single muscles or muscle groups in this disease. Methods: Histopathology, gene expression profiling and real time PCR were performed on biopsies from FSHD muscles with different MRI pattern (T1-weighted normal/T2-STIR normal and T1-weighted normal/T2-STIR hyperintense). Data were compared with those from inflammatory myopathies, dysferlinopathies and normal controls. In order to validate obtained results, two additional FSHD samples with different MRI pattern were analyzed. Results: Myopathic and inflammatory changes characterized T2-STIR hyperintense FSHD muscles, at variance with T2-STIR normal muscles. These two states could be easily distinguished from each other by their transcriptional profile. The comparison between T2-STIR hyperintense FSHD muscles and inflammatory myopathy muscles showed peculiar changes, although many alterations were shared among these conditions. Conclusions: At the single muscle level, different stages of the disease correspond to the two MRI patterns. T2-STIR hyperintense FSHD muscles are more similar to inflammatory myopathies than to T2-STIR normal FSHD muscles or other muscular dystrophies, and share with them upregulation of genes involved in innate and adaptive immunity. Our data suggest that selective inflammation, together with perturbation in biological processes such as neoangiogenesis, lipid metabolism and adipokine production, may contribute to the sequential bursts of muscle degeneration that involve individual muscles in an asynchronous manner in this disease.

AB - Background: Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies and is characterized by a non-conventional genetic mechanism activated by pathogenic D4Z4 repeat contractions. By muscle Magnetic Resonance Imaging (MRI) we observed that T2-short tau inversion recovery (T2-STIR) sequences identify two different conditions in which each muscle can be found before the irreversible dystrophic alteration, marked as T1-weighted sequence hyperintensity, takes place. We studied these conditions in order to obtain further information on the molecular mechanisms involved in the selective wasting of single muscles or muscle groups in this disease. Methods: Histopathology, gene expression profiling and real time PCR were performed on biopsies from FSHD muscles with different MRI pattern (T1-weighted normal/T2-STIR normal and T1-weighted normal/T2-STIR hyperintense). Data were compared with those from inflammatory myopathies, dysferlinopathies and normal controls. In order to validate obtained results, two additional FSHD samples with different MRI pattern were analyzed. Results: Myopathic and inflammatory changes characterized T2-STIR hyperintense FSHD muscles, at variance with T2-STIR normal muscles. These two states could be easily distinguished from each other by their transcriptional profile. The comparison between T2-STIR hyperintense FSHD muscles and inflammatory myopathy muscles showed peculiar changes, although many alterations were shared among these conditions. Conclusions: At the single muscle level, different stages of the disease correspond to the two MRI patterns. T2-STIR hyperintense FSHD muscles are more similar to inflammatory myopathies than to T2-STIR normal FSHD muscles or other muscular dystrophies, and share with them upregulation of genes involved in innate and adaptive immunity. Our data suggest that selective inflammation, together with perturbation in biological processes such as neoangiogenesis, lipid metabolism and adipokine production, may contribute to the sequential bursts of muscle degeneration that involve individual muscles in an asynchronous manner in this disease.

UR - http://www.scopus.com/inward/record.url?scp=84862227698&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862227698&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0038779

DO - 10.1371/journal.pone.0038779

M3 - Article

C2 - 22719944

AN - SCOPUS:84862227698

VL - 7

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 6

M1 - e38779

ER -