037 Fibroblast growth factor – binding protein cDNA and truncated variants are active in diabetic wound healing

Abstract

Fibroblast growth factor – binding protein (FGF‐BP) is a secreted protein that appears to function as a low affinity heparin –binding protein. FGF‐BP binds to FGF‐1 and ‐2 in a non‐covalent, reversible manner to mobilize and solubilize these growth factors from their storage sites in the extracellular matrix. FGF‐BP is involved in both developmental and adult tissue homeostasis as well as in angiogenesis and tumorogenesis involving FGF‐1/2. FGF‐BP is overexpressed in several tumor types: head and neck, skin, cervical, and lung cancer, squamous cell carcinoma, and colon and breast adenocarcinoma. To establish the effect of FGF‐BP on wound healing, several forms of FGF‐BP cDNA were administered by particle‐mediated gene transfer into various animal wound models using the gene gun (Bio‐Rad). In a rat incisional wound model, gene gun cDNA delivery of full length FGF‐BP at the time of surgery produced a 117% increase of wound strength in diabetic rats at 10d, although the relative increase did not reach statistical significance (P < 0.08). Two truncated variants of FGF‐BP (pFGFbp10 and 17) were also administered in the rat incisional wound model by gene gun technique. pFGFbp17 increased the wound strength in diabetic rat 129%(p < 0.03), and the relative increase reach statistical significance (P < 0.008). In the rabbit ear ulcer model, particle‐mediated transduction of full length FGF‐BP increased collagen content by 195% and wound closure rate 38% at 10d post‐surgery. These findings show that FGF‐BP gene overexpression has a greater relative effect on wound healing in the diabetic rat model. The cDNA also had a significant effect in a rabbit excisional wound model that depended on granulation tissue formation. Truncated forms of the molecule may have higher therapeutic potency. FGF‐BP has an important role in FGF‐1/2 mobilization and macrophage functions, and FGF‐BP gene therapy for wound healing can improve the process by stimulating angiogenesis, epithelization and collagen synthesis in target tissue.