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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2008-12-8
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:volume
1780
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1432-40
pubmed:meshHeading
pubmed-meshheading:18760333-Amino Acid Sequence, pubmed-meshheading:18760333-Animals, pubmed-meshheading:18760333-Cell Line, pubmed-meshheading:18760333-Cell Proliferation, pubmed-meshheading:18760333-Fibroblast Growth Factor 1, pubmed-meshheading:18760333-Fibroblast Growth Factor 2, pubmed-meshheading:18760333-Gamma Rays, pubmed-meshheading:18760333-Heparin, pubmed-meshheading:18760333-Intestine, Small, pubmed-meshheading:18760333-Keratinocytes, pubmed-meshheading:18760333-Mice, pubmed-meshheading:18760333-Mice, Inbred BALB C, pubmed-meshheading:18760333-Molecular Sequence Data, pubmed-meshheading:18760333-Protein Folding, pubmed-meshheading:18760333-Radiation Injuries, Experimental, pubmed-meshheading:18760333-Radiation-Protective Agents, pubmed-meshheading:18760333-Receptors, Fibroblast Growth Factor, pubmed-meshheading:18760333-Recombinant Fusion Proteins, pubmed-meshheading:18760333-Solutions, pubmed-meshheading:18760333-Trypsin, pubmed-meshheading:18760333-Whole-Body Irradiation
pubmed:year
2008
pubmed:articleTitle
An FGF1:FGF2 chimeric growth factor exhibits universal FGF receptor specificity, enhanced stability and augmented activity useful for epithelial proliferation and radioprotection.
pubmed: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.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't