title: An FGF1:FGF2 chimeric growth factor exhibits universal FGF receptor specificity, enhanced stability and augmented activity useful for epithelial proliferation and radioprotection.
abstract: Structural instability of wild-type fibroblast growth factor (FGF)-1 and its dependence on exogenous heparin for optimal activity diminishes its potential utility as a therapeutic agent. Here we evaluated FGFC, an FGF1:FGF2 chimeric protein, for its receptor affinity, absolute heparin-dependence, stability and potential clinical applicability. Using BaF3 transfectants overexpressing each FGF receptor (FGFR) subtype, we found that, like FGF1, FGFC activates all of the FGFR subtypes (i.e., FGFR1c, FGFR1b, FGFR2c, FGFR2b, FGFR3c, FGFR3b and FGFR4) in the presence of heparin. Moreover, FGFC activates FGFRs even in the absence of heparin. FGFC stimulated keratinocytes proliferation much more strongly than FGF2, as would be expected from its ability to activate FGFR2b. FGFC showed greater structural stability, biological activity and resistance to trypsinization, and less loss in solution than FGF1 or FGF2. When FGFC was intraperitoneally administered to BALB/c mice prior to whole body gamma-irradiation, survival of small intestine crypts was significantly enhanced, as compared to control mice. These results suggest that FGFC could be useful in a variety of clinical applications, including promotion of wound healing and protection against radiation-induced damage.
authors.affiliation: Signaling Molecules Research Group, Neuroscience Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Motomura
authors.forename: Akiko
authors.initials: A
authors.lastname: Hagiwara
authors.forename: Akiko
authors.initials: A
authors.lastname: Komi-Kuramochi
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Hanyu
authors.forename: Emi
authors.initials: E
authors.lastname: Honda
authors.forename: Masashi
authors.initials: M
authors.lastname: Suzuki
authors.forename: Miho
authors.initials: M
authors.lastname: Kimura
authors.forename: Junko
authors.initials: J
authors.lastname: Oki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Asada
authors.forename: Nagako
authors.initials: N
authors.lastname: Sakaguchi
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Nakayama
authors.forename: Makoto
authors.initials: M
authors.lastname: Akashi
authors.forename: Toru
authors.initials: T
authors.lastname: Imamura