Heparin-like synthetic polymers, named RGTAs, mimic biological effects of heparin in vitro.
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.
Rouet
Vincent
V
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.
Meddahi-Pellé
Anne
A
Miao
Hua-Quan
HQ
Vlodavsky
Israel
I
Caruelle
Jean-Pierre
JP
Barritault
Denis
D
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
D003911:Dextrans; D016222:Fibroblast Growth Factor 2; D005966:Glucuronidase; D006493:Heparin; D011108:Polymers; D011994:Recombinant Proteins; D000099175:Heparanase; C475611:RG1192