RRC ID 43452
著者 Motomura K, Hagiwara A, Komi-Kuramochi A, Hanyu Y, Honda E, Suzuki M, Kimura M, Oki J, Asada M, Sakaguchi N, Nakayama F, Akashi M, Imamura T.
タイトル An FGF1:FGF2 chimeric growth factor exhibits universal FGF receptor specificity, enhanced stability and augmented activity useful for epithelial proliferation and radioprotection.
ジャーナル Biochim Biophys Acta
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.
巻・号 1780(12)
ページ 1432-40
公開日 2008-12-1
DOI 10.1016/j.bbagen.2008.08.001
PII S0304-4165(08)00180-3
PMID 18760333
MeSH Amino Acid Sequence Animals Cell Line Cell Proliferation / drug effects Fibroblast Growth Factor 1 / chemistry Fibroblast Growth Factor 1 / genetics* Fibroblast Growth Factor 2 / chemistry Fibroblast Growth Factor 2 / genetics* Gamma Rays Heparin / pharmacology Intestine, Small / drug effects Intestine, Small / pathology Intestine, Small / radiation effects Keratinocytes / cytology Keratinocytes / drug effects Mice Mice, Inbred BALB C Molecular Sequence Data Protein Folding Radiation Injuries, Experimental / pathology Radiation Injuries, Experimental / prevention & control Radiation-Protective Agents / chemistry Radiation-Protective Agents / pharmacology* Receptors, Fibroblast Growth Factor / agonists* Recombinant Fusion Proteins / chemistry Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / pharmacology* Solutions Trypsin / metabolism Whole-Body Irradiation
IF 3.411
引用数 31
WOS 分野 BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 Ba/F3(RCB0805)