Rouet Vincent, Meddahi-Pellé Anne, Miao Hua-Quan, Vlodavsky Israel, Caruelle Jean-Pierre, Barritault Denis
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.
J Biomed Mater Res A. 2006 Sep 15;78(4):792-7. doi: 10.1002/jbm.a.30723.
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.
一类经过工程改造以保护和稳定肝素结合生长因子（HBGFs）的生物聚合物，在几种体内组织修复模型中作为伤口愈合剂表现出显著特性，以至于受损组织几乎能恢复其初始外观和特性。这些聚合物被命名为RGTA（再生剂），并被认为在体内通过提高损伤部位HBGFs的生物利用度来发挥作用。为了支持这一假设，我们研究了RGTA与作为HBGFs范例的FGF-2及其高亲和力和低亲和力受体的相互作用，以及其抑制乙酰肝素酶活性的能力。我们发现，RGTA与肝素相当，因为它有利于FGF-2与FGFR-1结合以及FGF-2二聚化，并增强FGF-2诱导的促有丝分裂活性。此外，我们表明RGTA可抑制乙酰肝素酶从细胞外基质储存位点释放FGF-2。我们的数据提供了新的证据，支持RGTA可能在体内通过增强HBGF活性以及通过保护基质低亲和力硫酸乙酰肝素免受乙酰肝素酶快速降解来保持HBGF的可用性而发挥作用。
