Comparison of expression profiles of several fibroblast growth factor receptors in the mouse jejunum: suggestive evidence for a differential radioprotective effect among major FGF family members and the potency of FGF1.
Several members of the fibroblast growth factor (FGF) family have the potential to protect the intestine against the side effects of radiation therapy. FGF1 is capable of signaling through all subtypes of FGF receptors (FGFRs), whereas FGF7 and FGF10 activate only the epithelial-specific subtype, FGFR2IIIb (FGFR2b). The present study compared the protective activity of FGF1, FGF7 and FGF10 and examined the profiles of FGFR expression in the jejunum of BALB/c mice given total-body irradiation (TBI) with gamma rays. TBI caused drastic increases in FGFR1-4 transcript levels in the jejunum. However, FGFR2b protein temporarily decreased at 12 and 24 h after irradiation. FGF1 pretreatment minimized the number of apoptotic cells in jejunal crypts at 16 and 24 h after irradiation and increased crypt survival most effectively. In addition, pretreatment with FGF7 or FGF10 decreased FGFR1 transcript levels. The greater effectiveness of FGF1 to enhance crypt survival was also observed even when each FGF was administered 1 h after irradiation. These findings indicate that FGF1 is more potent than FGF7 or FGF10 for protection of the intestine against radiation exposure and suggest that the profiles of FGFR expression in the intestine favor the FGF1 signaling pathway before and during the initial period after irradiation.
Hagiwara
Akiko
A
Department of Radiation Emergency Medicine, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
Nakayama
Fumiaki
F
Motomura
Kaori
K
Asada
Masahiro
M
Suzuki
Masashi
M
Imamura
Toru
T
Akashi
Makoto
M
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D051526:Fibroblast Growth Factor 10 / Q000494:pharmacology; D051523:Fibroblast Growth Factor 7 / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D005720:Gamma Rays / Q000009:adverse effects*; D007583:Jejunum / Q000378:metabolism* / Q000528:radiation effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000378:metabolism; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology
C496464:Fgf10 protein, mouse; C496454:Fgf7 protein, mouse; D051526:Fibroblast Growth Factor 10; D011837:Radiation-Protective Agents; D011993:Recombinant Fusion Proteins; D016220:Fibroblast Growth Factor 1; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; C496349:Fgfr1 protein, mouse; C496354:Fgfr2 protein, mouse; C496366:Fgfr3 protein, mouse; C496372:Fgfr4 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3; D051499:Receptor, Fibroblast Growth Factor, Type 4