title: Increase in decorin and biglycan in Duchenne Muscular Dystrophy: role of fibroblasts as cell source of these proteoglycans in the disease.
abstract: Fibrosis is a common pathological feature observed in muscles of patients with Duchenne muscular dystrophy (DMD). Biglycan and decorin are small chondroitin/dermatan sulfate proteoglycans in the muscle extracellular matrix (ECM) that belong to the family of structurally related proteoglycans called small leucine-rich repeat proteins. Decorin is considered an anti-fibrotic agent, preventing the process by blocking TGF-beta activity. There is no information about their expression in DMD patients. We found an increased amount of both proteoglycans in the ECM of skeletal muscle biopsies obtained from DMD patients. Both biglycan and decorin were augmented in the perimysium of muscle tissue, but only decorin increased in the endomysium as seen by immunohistochemical analyses. Fibroblasts were isolated from explants obtained from muscle of DMD patients and the incorporation of radioactive sulfate showed an increased synthesis of both decorin and biglycan in cultured fibroblasts compared to controls. The size of decorin and biglycan synthesized by DMD and control fibroblasts seems to be similar in size and anion charge. These findings show that decorin and biglycan are increased in DMD skeletal muscle and suggest that fibroblasts would be, at least, one source for these proteoglycans likely playing a role in the muscle response to dystrophic cell damage.
authors.affiliation: Departamento de Neurología, Facultad de Medicina. Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fadic
authors.forename: Valeria
authors.initials: V
authors.lastname: Mezzano
authors.forename: Karin
authors.initials: K
authors.lastname: Alvarez
authors.forename: Daniel
authors.initials: D
authors.lastname: Cabrera
authors.forename: Jenny
authors.initials: J
authors.lastname: Holmgren
authors.forename: Enrique
authors.initials: E
authors.lastname: Brandan
mesh_terms: D058578:Biglycan; D001706:Biopsy; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism*; D005355:Fibrosis / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007422:Intestines / Q000473:pathology; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009132:Muscles / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism* / Q000473:pathology; D011509:Proteoglycans / Q000096:biosynthesis / Q000737:chemistry*
chemical_list: C546884:BGN protein, human; D058578:Biglycan; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans