Enhancement of PDGF-BB mitogenic activity on human dermal fibroblasts by biospecific dextran derivatives.
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.
Vercoutter-Edouart
Anne-Sophie
AS
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
Dubreucq
Guy
G
Vanhoecke
Barbara
B
Rigaut
Christelle
C
Renaux
François
F
Dahri-Correia
Latifa
L
Lemoine
Jérôme
J
Bracke
Marc
M
Michalski
Jean-Claude
JC
Correia
José
J
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
D003911:Dextrans; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin