title: Inhibitory effects of glycosaminoglycans on basal and stimulated transforming growth factor-β1 expression in mesangial cells: biochemical and structural considerations.
abstract: A number of glycosaminoglycan (GAG) species related to heparin, dermatan sulfate (DeS) and chondroitin sulfate were tested for their ability to interfere with the physiological expression and/or pathological overexpression of the TGF-β1 gene. The influence of the molecular weight, molecular weight distribution, degree of sulfation and location of the sulfate groups was examined in an attempt to unveil fine relationships between structure and activity. The nature of the polysaccharide plays a major part, heparins proving able to inhibit both basal and stimulated TGF-β1 gene expression, DeSs being essentially inactive and chondroitin sulfates only inhibiting stimulated TGF-β1 gene expression. Within this frame, the particular physical and chemical properties of some GAGs appear to further modulate TGF-β1 gene response. Judging from our investigation, chondroitin sulfates seem the most promising for potential pharmacological applications in disorders characterized by fibrogenic TGF-β1 overexpression.
authors.affiliation: Department of Pharmaceutical Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bacilieri
authors.forename: Annamaria
authors.initials: A
authors.lastname: Naggi
authors.forename: Monica
authors.initials: M
authors.lastname: Ceol
authors.forename: Erwin D
authors.initials: ED
authors.lastname: Schleicher
authors.forename: Enrica
authors.initials: E
authors.lastname: Tosetto
authors.forename: Maura
authors.initials: M
authors.lastname: Comoli
authors.forename: Giangiacomo
authors.initials: G
authors.lastname: Torri
authors.forename: Stefano
authors.initials: S
authors.lastname: Moro
authors.forename: Manlio
authors.initials: M
authors.lastname: Palumbo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Gambaro
mesh_terms: D000818:Animals; D002236:Carbohydrate Conformation; D002478:Cells, Cultured; D006025:Glycosaminoglycans / Q000737:chemistry / Q000494:pharmacology*; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013329:Structure-Activity Relationship; D013552:Swine; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D006025:Glycosaminoglycans; D053773:Transforming Growth Factor beta1