title: Enhancement of PDGF-BB mitogenic activity on human dermal fibroblasts by biospecific dextran derivatives.
abstract: Dextran derivatives are biosynthetic polyanionic polymers which exert some of the heparin properties such as regulating the activity of several heparin-binding growth factors. Based on a reproducible synthetic procedure, we have synthesized a new generation of dextran derivatives named dextran methylcarboxylate benzylamide sulfate (DMCBSu). Here we investigated the ability of a library of well-characterized DMCBSu to interact with platelet-derived growth factor-BB (PDGF-BB), which has essential roles during wound healing. Using gel mobility shift assay, our results indicate that benzylamide and sulfate groups act synergically to bind to PDGF-BB. Furthermore we show that depending on their chemical composition, functionalized dextrans are able to potentiate the mitogenic activity of PDGF-BB on human dermal fibroblasts. This enhancing effect is accompanied with changes in PDGF-BB-induced signaling events, as determined by the use of specific inhibitors and by western blot. Our results suggest that the use of such biopolymers combined with a local administration of the growth factor could increase the efficiency of the biomolecule activity in future therapeutic strategies.
authors.affiliation: Unité de Glycobiologie Structurale et Fonctionnelle, UMR USTL/CNRS n 8576, bâtiment C9, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France. anne-sophie.vercoutter@univ-lille1.fr
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Vercoutter-Edouart
authors.forename: Guy
authors.initials: G
authors.lastname: Dubreucq
authors.forename: Barbara
authors.initials: B
authors.lastname: Vanhoecke
authors.forename: Christelle
authors.initials: C
authors.lastname: Rigaut
authors.forename: François
authors.initials: F
authors.lastname: Renaux
authors.forename: Latifa
authors.initials: L
authors.lastname: Dahri-Correia
authors.forename: Jérôme
authors.initials: J
authors.lastname: Lemoine
authors.forename: Marc
authors.initials: M
authors.lastname: Bracke
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Michalski
authors.forename: José
authors.initials: J
authors.lastname: Correia
mesh_terms: D000077214:Becaplermin; D002460:Cell Line; D003911:Dextrans / Q000138:chemical synthesis / Q000737:chemistry*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008938:Mitosis; D010982:Platelet-Derived Growth Factor / Q000737:chemistry* / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D012867:Skin / Q000166:cytology; D014945:Wound Healing / Q000187:drug effects
chemical_list: D003911:Dextrans; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin