Abstract
The Fibroblast growth factor (FGF) family polypeptides regulate cell proliferation, differentiation, and metabolisms. FGFs need heparan sulfate (HS)/ heparin as a co-factor to activate FGF receptors (FGFRs). Although FGF1 and FGF2 are structurally related, they are different in receptor specificity and heparin dependence; activity of FGF1 is more dependent on exogenous heparin than FGF2. We previously reported systematic construction and expression of various forms of FGF1/FGF2 chimeric proteins in an attempt to address structure-activity relationships as well as creating useful molecules. One of those, designated FGF-C, in which residues 44-86 of FGF1 was substituted with the corresponding region of FGF2, was studied in the present study. The FGF-C was analyzed for its heparin dependence, receptor specificity and protective potential against radiation-induced damage. A cell line that has neither endogenous HS nor FGFR was stably transfected with various types of FGFR, and was used to evaluate their proliferation in response to FGF1 and FGF-C in the presence and absence of exogenous heparin. Not only FGF-C demonstrated FGF1-like receptor specificity and potency in the presence of heparin, its activity in the absence of heparin was more potent than FGF1. When C3H mice were intraperitoneally administered with FGF-C prior to whole body γ-irradiation (10Gy), it stimulated regeneration of small intestine crypts with a potency similar to FGF1. These results suggest clinical usefulness of FGF-C for its protective potential against radiation-induced damage.
