Brain Advance Access originally published online on September 23, 2005
Brain 2005 128(11):2546-2555; doi:10.1093/brain/awh635
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Decorin and biglycan expression is differentially altered in several muscular dystrophies
1 Division of Neuromuscular Diseases and Neuroimmunology, Istituto Nazionale Neurologico "C. Besta", Milano, 2 Department of Neurological and Psychiatric Sciences, University of Padova, Padova and 3 Department of Neurological Sciences, University of Milano, Ospedale Maggiore Policlinico, Milano, Italy
Correspondence to: Marina Mora, PhD, Division of Neuromuscular Diseases, Muscle Cell Biology Lab, National Neurological Institute "C. Besta", Bicocca Laboratories, Via Temolo 4, 20126 Milano, Italy E-mail: mmora{at}istituto-besta.it
Biglycan and decorin are small extracellular proteoglycans that interact with cytokines, whose activity they may modulate, and with matrix proteins, particularly collagens. To better understand their role in muscle fibrosis, we investigated expression of decorin and biglycan transcripts and protein in muscle of several forms of muscular dystrophy, and also expression of perlecan, an extracellular proteoglycan unrelated to collagen deposition. In Duchenne muscular dystrophy (DMD) and LAMA2-mutated congenital muscular dystrophy (MDC1A) we also quantitated transcript levels of the profibrotic cytokine TGF-ß1. We examined muscle biopsies from nine DMD patients, aged 2–8 years; 14 BMD (Becker muscular dystrophy) patients (nine aged 1–5 years; five aged 30–37 years); four MDC1A patients (aged 2–7 years); six dysferlin-deficient patients (aged 19–53 years) with mutation ascertained in two, and normal expression of proteins related to limb girdle muscular dystrophies in the others; 10 sarcoglycan-deficient patients: seven with 
-sarcoglycan mutation, two with ß-sarcoglycan mutation and one with 
-sarcoglycan mutation (five aged 8–15 years; five aged 26–43 years); and nine children (aged 1–6 years) and 12 adults (aged 16–61 years) suspected of neuromuscular disease, but who had normal muscle on biopsy. Biglycan mRNA levels varied in DMD and MDC1A depending on the quantitation method, but were upregulated in BMD, sarcoglycanopathies and dysferlinopathy. Decorin mRNA was significantly downregulated in DMD and MDC1A, whereas TGF-ß1 was significantly upregulated. Decorin mRNA was normal in paediatric BMD, but upregulated in adult BMD, sarcoglycanopathies and dysferlinopathy. Perlecan transcript levels were similar to those of age-matched controls in all disease groups. By immunohistochemistry, decorin and biglycan were mainly localized in muscle connective tissue; their presence increased in relation to increased fibrosis in all dystrophic muscle. By visual inspection, decorin bands on immunoblot did not differ from those of age-matched controls in all patient groups. However, when the intensity of the bands was quantitated against vimentin and normalized against sarcomeric actin, in DMD and MDC1A the ratio of band intensities was significantly lower than in age-matched controls. Variations in the transcript and protein levels of these proteoglycans in different muscular dystrophies probably reflect the variable disruption of extracellular matrix organization that occurs in these diseases. The significantly lowered decorin levels in DMD and MDC1A may be related to the increased TGF-ß1 levels, suggesting a therapeutic role of decorin in these severe dystrophies.
Key Words: proteoglycans; fibrosis; muscular dystrophy; decorin; biglycan
Abbreviations: BMD = Becker muscular dystrophy; DAPs = dystrophin-associated proteins; DMD = Duchenne muscular dystrophy; TGF-ß = transforming growth factor-ß
Received February 7, 2005. Revised August 10, 2005. Accepted August 22, 2005.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Alexakis, T. Partridge, and G. Bou-Gharios Implication of the satellite cell in dystrophic muscle fibrosis: a self-perpetuating mechanism of collagen overproduction Am J Physiol Cell Physiol, August 1, 2007; 293(2): C661 - C669. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Pescatori, A. Broccolini, C. Minetti, E. Bertini, C. Bruno, A. D'amico, C. Bernardini, M. Mirabella, G. Silvestri, V. Giglio, et al. Gene expression profiling in the early phases of DMD: a constant molecular signature characterizes DMD muscle from early postnatal life throughout disease progression FASEB J, April 1, 2007; 21(4): 1210 - 1226. [Abstract] [Full Text] [PDF]
|
|