Decorin and biglycan expression is differentially altered in several muscular dystrophies

Simona Zanotti, Tiziana Negri, Cristina Cappelletti, Pia Bernasconi, Eleonora Canioni, Claudia Di Blasi, Elena Pegoraro, Corrado Angelini, Patrizia Ciscato, Alessandro Prelle, Renato Mantegazza, Lucia Morandi, Marina Mora

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

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-β1. 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 α-sarcoglycan mutation, two with β-sarcoglycan mutation and one with γ-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-β1 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-β1 levels, suggesting a therapeutic role of decorin in these severe dystrophies.

Original languageEnglish
Pages (from-to)2546-2555
Number of pages10
JournalBrain
Volume128
Issue number11
DOIs
Publication statusPublished - Nov 2005

Fingerprint

Biglycan
Decorin
Duchenne Muscular Dystrophy
Muscular Dystrophies
Sarcoglycans
Sarcoglycanopathies
Proteoglycans
Muscles
Mutation
Messenger RNA
Fibrosis
Collagen
Limb-Girdle Muscular Dystrophies
Cytokines
Biopsy
Neuromuscular Diseases
Proteins
Muscle Proteins
Vimentin
Connective Tissue

Keywords

  • Biglycan
  • Decorin
  • Fibrosis
  • Muscular dystrophy
  • Proteoglycans

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Decorin and biglycan expression is differentially altered in several muscular dystrophies. / Zanotti, Simona; Negri, Tiziana; Cappelletti, Cristina; Bernasconi, Pia; Canioni, Eleonora; Di Blasi, Claudia; Pegoraro, Elena; Angelini, Corrado; Ciscato, Patrizia; Prelle, Alessandro; Mantegazza, Renato; Morandi, Lucia; Mora, Marina.

In: Brain, Vol. 128, No. 11, 11.2005, p. 2546-2555.

Research output: Contribution to journalArticle

Zanotti, S, Negri, T, Cappelletti, C, Bernasconi, P, Canioni, E, Di Blasi, C, Pegoraro, E, Angelini, C, Ciscato, P, Prelle, A, Mantegazza, R, Morandi, L & Mora, M 2005, 'Decorin and biglycan expression is differentially altered in several muscular dystrophies', Brain, vol. 128, no. 11, pp. 2546-2555. https://doi.org/10.1093/brain/awh635
Zanotti S, Negri T, Cappelletti C, Bernasconi P, Canioni E, Di Blasi C et al. Decorin and biglycan expression is differentially altered in several muscular dystrophies. Brain. 2005 Nov;128(11):2546-2555. https://doi.org/10.1093/brain/awh635
Zanotti, Simona ; Negri, Tiziana ; Cappelletti, Cristina ; Bernasconi, Pia ; Canioni, Eleonora ; Di Blasi, Claudia ; Pegoraro, Elena ; Angelini, Corrado ; Ciscato, Patrizia ; Prelle, Alessandro ; Mantegazza, Renato ; Morandi, Lucia ; Mora, Marina. / Decorin and biglycan expression is differentially altered in several muscular dystrophies. In: Brain. 2005 ; Vol. 128, No. 11. pp. 2546-2555.
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AU - Zanotti, Simona

AU - Negri, Tiziana

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AU - Canioni, Eleonora

AU - Di Blasi, Claudia

AU - Pegoraro, Elena

AU - Angelini, Corrado

AU - Ciscato, Patrizia

AU - Prelle, Alessandro

AU - Mantegazza, Renato

AU - Morandi, Lucia

AU - Mora, Marina

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N2 - 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-β1. 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 α-sarcoglycan mutation, two with β-sarcoglycan mutation and one with γ-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-β1 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-β1 levels, suggesting a therapeutic role of decorin in these severe dystrophies.

AB - 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-β1. 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 α-sarcoglycan mutation, two with β-sarcoglycan mutation and one with γ-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-β1 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-β1 levels, suggesting a therapeutic role of decorin in these severe dystrophies.

KW - Biglycan

KW - Decorin

KW - Fibrosis

KW - Muscular dystrophy

KW - Proteoglycans

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