title: Heparin-like synthetic polymers, named RGTAs, mimic biological effects of heparin in vitro.
abstract: A family of biopolymers engineered to protect and stabilize heparin binding growth factors (HBGFs) show remarkable properties as wound healing agents in several in vivo tissue repair models to the extend that damaged tissues would recover almost its initial aspect and properties. These polymers where named RGTA for regenerating agents and proposed to act in vivo by enhancing the bioavailability of HBGFs at the site of the injury. To provide support for this hypothesis, we studied interaction of RGTA with FGF-2, taken as the paradigm of HBGFs, and its high- and low-affinity receptors as well as its ability to inhibit heparanase activity. We show that RGTA is comparable to heparin as it favors FGF-2 binding to FGFR-1 and FGF-2 dimerization and potentiates FGF-2-induced mitogenic activity. Furthermore, we show that RGTA inhibits the release of FGF-2 from its extracellular matrix storage sites by heparanase. Our data provide new evidence to support that RGTA may act in vivo both by enhancing HBGF activity and preserving HBGF availability by protecting the matrix low affinity heparan sulfates from rapid heparanase degradation.
authors.affiliation: Laboratoire de Recherche sur la Croissance, la Réparation et la Régénération Tissulaire (CRRET), UMR 7149, Université Paris XII-Val de Marne, 61 avenue du général de Gaulle, 94010 Créteil Cedex, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Rouet
authors.forename: Anne
authors.initials: A
authors.lastname: Meddahi-Pellé
authors.forename: Hua-Quan
authors.initials: HQ
authors.lastname: Miao
authors.forename: Israel
authors.initials: I
authors.lastname: Vlodavsky
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Caruelle
authors.forename: Denis
authors.initials: D
authors.lastname: Barritault
mesh_terms: D000818:Animals; D016466:CHO Cells; D002417:Cattle; D002478:Cells, Cultured; D006224:Cricetinae; D003911:Dextrans / Q000494:pharmacology; D019281:Dimerization; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology*; D018716:Molecular Mimicry; D011108:Polymers / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D000099175:Heparanase
chemical_list: D003911:Dextrans; D016222:Fibroblast Growth Factor 2; D005966:Glucuronidase; D006493:Heparin; D011108:Polymers; D011994:Recombinant Proteins; D000099175:Heparanase; C475611:RG1192