title: Augmented synthesis and differential localization of heparan sulfate proteoglycans in Duchenne muscular dystrophy.
abstract: Muscular dystrophies are characterized by continuous cycles of degeneration and regeneration that result in extensive fibrosis and a progressive diminution of muscle mass. Cell surface heparan sulfate proteoglycans are found almost ubiquitously on the surface and in the extracellular matrix (ECM) of mammalian cells. These macromolecules interact with a great variety of ligands, including ECM constituents, adhesion molecules, and growth factors. In this study, we evaluated the expression and localization of three heparan sulfate proteoglycans in the biopsies of Duchenne muscular dystrophy (DMD) patients. Through SDS-PAGE analyses followed by specific identification of heparitinase-digested proteins with an anti-Delta-heparan sulfate specific monoclonal antibodies, we observed an increase of three forms of heparan sulfate proteoglycans, corresponding to perlecan, syndecan-3, and glypican-1. Immunohistochemistry analyses indicated a differential localization for these proteoglycans: glypican-1 and perlecan were found mainly associated to ECM structures, while syndecan-3 was associated to muscle fibers. These results suggest that the amount of specific heparan sulfate proteoglycans is augmented in skeletal muscle in DMD patients presenting a differential localization.
authors.affiliation: Centro de Regulación y Patología, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, MIFAB, P. Universidad Católica de Chile, Santiago, Chile.
authors.forename: Karin
authors.initials: K
authors.lastname: Alvarez
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fadic
authors.forename: Enrique
authors.initials: E
authors.lastname: Brandan
mesh_terms: D002648:Child; D005109:Extracellular Matrix / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D053670:Syndecan-3
chemical_list: D019812:Heparan Sulfate Proteoglycans; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508301:SDC3 protein, human; D053670:Syndecan-3; C071927:perlecan