Abstract
Fibroblast growth factors (FGFs) play important roles in numerous biological events such as angiogenesis and wound repair.FGFs need heparan sulfate / heparin as a co-factor to activate FGF receptor (FGFR). FGF7, one of FGFR2b ligands, has been approved as a remedy for radiotherapy-induced oral mucositis. We previously studied the protective activity of FGF1, FGF7, and FGF10, as ligands for FGFR2b, and reported that FGF1 protects the jejunum from radiation-induced injuries more effectively than FGF7 and FGF10. However, the structural instability of wild-type FGF1 and its dependence on exogenous heparin diminish its potential for practical use. Although FGF2 is structurally related to FGF1, its activity is more independent on exogenous heparin than FGF1.We have created an FGF1:FGF2 chimera (FGFC) and found its activity in the absence of heparin was more potent than FGF1. This study aimed at evaluating the protective activity of FGFC against radiation-induced intestinal damage. Receptor specificity analysis showed that FGFC was able to activate all of the FGFR subtypes similar to FGF1. When FGFC was administered with heparin intraperitoneally to mice at 24 h before total body irradiation, it increased small intestinal crypts survival with a potency similar to FGF1. Whereas it was even superior to FGF1 when administered without heparin. Finally, the effectiveness of FGFC was also observed without heparin when it was administered 24 h after irradiation. These findings suggest that FGFC is useful in clinical applications for both prevention and post-treatment of radiation injuries.
