title: Decorin and biglycan expression is differentially altered in several muscular dystrophies.
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-beta1. 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 alpha-sarcoglycan mutation, two with beta-sarcoglycan mutation and one with gamma-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-beta1 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-beta1 levels, suggesting a therapeutic role of decorin in these severe dystrophies.
authors.affiliation: Division of Neuromuscular Diseases and Neuroimmunology, Istituto Nazionale Neurologico "C. Besta", Milano, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Zanotti
authors.forename: Tiziana
authors.initials: T
authors.lastname: Negri
authors.forename: Cristina
authors.initials: C
authors.lastname: Cappelletti
authors.forename: Pia
authors.initials: P
authors.lastname: Bernasconi
authors.forename: Eleonora
authors.initials: E
authors.lastname: Canioni
authors.forename: Claudia
authors.initials: C
authors.lastname: Di Blasi
authors.forename: Elena
authors.initials: E
authors.lastname: Pegoraro
authors.forename: Corrado
authors.initials: C
authors.lastname: Angelini
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ciscato
authors.forename: Alessandro
authors.initials: A
authors.lastname: Prelle
authors.forename: Renato
authors.initials: R
authors.lastname: Mantegazza
authors.forename: Lucia
authors.initials: L
authors.lastname: Morandi
authors.forename: Marina
authors.initials: M
authors.lastname: Mora
mesh_terms: D000293:Adolescent; D000328:Adult; D058578:Biglycan; D002648:Child; D002675:Child, Preschool; D024142:Collagen Type VI / Q000378:metabolism; D058575:Decorin; D016326:Extracellular Matrix Proteins; D015870:Gene Expression; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D009136:Muscular Dystrophies / Q000378:metabolism*; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
chemical_list: C546884:BGN protein, human; D058578:Biglycan; D024142:Collagen Type VI; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D019812:Heparan Sulfate Proteoglycans; D011509:Proteoglycans; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C071927:perlecan