POST TREATMENT WITH AN FGF CHIMERIC GROWTH FACTOR ENHANCES EPITHELIAL CELL PROLIFERATION TO IMPROVE RECOVERY FROM RADIATION-INDUCED INTESTINAL DAMAGE

被引:15
作者
Nakayama, Fumiaki [1 ]
Hagiwara, Akiko
Umeda, Sachiko
Asada, Masahiro [2 ]
Goto, Megumi [2 ]
Oki, Junko [2 ]
Suzuki, Masashi [2 ]
Imamura, Toru [2 ]
Akashi, Makoto
机构
[1] Natl Inst Radiol Sci, Dept Radiat Emergency Med, Inage Ku, Chiba 2638555, Japan
[2] Natl Inst Adv Ind Sci & Technol, Biomed Res Inst, Signaling Mol Res Grp, Tsukuba, Ibaraki, Japan
来源
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS | 2010年 / 78卷 / 03期
关键词
Chimeric protein; Fibroblast growth factor; Intestine; Proliferation; Radiation damage; FACTOR-I; GASTROINTESTINAL SYNDROME; NUCLEAR-LOCALIZATION; HALF-LIFE; HEPARIN; MICE; IDENTIFICATION; ACTIVATION; APOPTOSIS; SURVIVAL;
D O I
10.1016/j.ijrobp.2010.04.045
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: A fibroblast growth factor (FGF) 1-FGF2 chimera (FGFC) was created previously and showed greater structural stability than FGF1. This chimera was capable of stimulating epithelial cell proliferation much more strongly than FGF1 or FGF2 even without heparin. Therefore FGFC was expected to have greater biologic activity in vivo. This study evaluated and compared the protective activity of FGFC and FGF1 against radiation-induced intestinal injuries. Methods and Materials: We administered FGFC and FGF1 intraperitoneally to BALB/c mice 24 h before or after total-body irradiation (TBI). The numbers of surviving crypts were determined 3.5 days after TBI with gamma rays at doses ranging from 8 to 12 Gy. Results: The effect of FGFC was equal to or slightly superior to FGF1 with heparin. However, FGFC was significantly more effective in promoting crypt survival than FGF1 (p < 0.01) when 10 mu g of each FGF was administered without heparin before irradiation. In addition, FGFC was significantly more effective at promoting crypt survival (p < 0.05) than FGF1 even when administered without heparin at 24 h after TBI at 10, 11, or 12 Gy. We found that FGFC post treatment significantly promoted 5-bromo-2'-deoxyuridine incorporation into crypts and increased crypt depth, resulting in more epithelial differentiation. However, the number of apoptotic cells in FGFC-treated mice decreased to almost the same level as that in FGF1-treated mice. Conclusions: These findings suggest that FGFC strongly enhanced radioprotection with the induction of epithelial proliferation without exogenous heparin after irradiation and is useful in clinical applications for both the prevention and post treatment of radiation injuries. (C) 2010 Elsevier Inc.
引用
收藏
页码:860 / 867
页数:8
相关论文
共 26 条
[1]   Identification of stem cells in small intestine and colon by marker gene Lgr5 [J].
Barker, Nick ;
van Es, Johan H. ;
Kuipers, Jeroen ;
Kujala, Pekka ;
van den Born, Maaike ;
Cozijnsen, Miranda ;
Haegebarth, Andrea ;
Korving, Jeroen ;
Begthel, Harry ;
Peters, Peter J. ;
Clevers, Hans .
NATURE, 2007, 449 (7165) :1003-U1
[2]   What causes the radiation gastrointestinal syndrome? Overview [J].
Brown, Martin .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2008, 70 (03) :799-800
[3]   EFFECT OF POLYANIONS ON THE UNFOLDING OF ACIDIC FIBROBLAST GROWTH-FACTOR [J].
BURKE, CJ ;
VOLKIN, DB ;
MACH, H ;
MIDDAUGH, CR .
BIOCHEMISTRY, 1993, 32 (25) :6419-6426
[4]   THE STRUCTURE OF HUMAN ACIDIC FIBROBLAST GROWTH-FACTOR AND ITS INTERACTION WITH HEPARIN [J].
COPELAND, RA ;
JI, HL ;
HALFPENNY, AJ ;
WILLIAMS, RW ;
THOMPSON, KC ;
HERBER, WK ;
THOMAS, KA ;
BRUNER, MW ;
RYAN, JA ;
MARQUISOMER, D ;
SANYAL, G ;
SITRIN, RD ;
YAMAZAKI, S ;
MIDDAUGH, CR .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1991, 289 (01) :53-61
[5]   Thermodynamic characterization of mutants of human fibroblast growth factor 1 with an increased physiological half-life [J].
Culajay, JF ;
Blaber, SI ;
Khurana, A ;
Blaber, M .
BIOCHEMISTRY, 2000, 39 (24) :7153-7158
[6]   HEPARIN POTENTIATES THE ACTION OF ACIDIC FIBROBLAST GROWTH-FACTOR BY PROLONGING ITS BIOLOGICAL HALF-LIFE [J].
DAMON, DH ;
LOBB, RR ;
DAMORE, PA ;
WAGNER, JA .
JOURNAL OF CELLULAR PHYSIOLOGY, 1989, 138 (02) :221-226
[7]   Enhanced anti-apoptosis and gut epithelium protection function of acidic fibroblast growth factor after cancelling of its mitogenic activity [J].
Fu, Xiao-Bing ;
Li, Xiao-Kun ;
Wang, Tong ;
Cheng, Biao ;
Sheng, Zhi-Yong .
WORLD JOURNAL OF GASTROENTEROLOGY, 2004, 10 (24) :3590-3596
[8]   HUMAN BRAIN-DERIVED ACIDIC AND BASIC FIBROBLAST GROWTH-FACTORS - AMINO TERMINAL SEQUENCES AND SPECIFIC MITOGENIC ACTIVITIES [J].
GIMENEZGALLEGO, G ;
CONN, G ;
HATCHER, VB ;
THOMAS, KA .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1986, 135 (02) :541-548
[9]   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 [J].
Hagiwara, Akiko ;
Nakayama, Fumiaki ;
Motomura, Kaori ;
Asada, Masahiro ;
Suzuki, Masashi ;
Imamura, Toru ;
Akashi, Makoto .
RADIATION RESEARCH, 2009, 172 (01) :58-65
[10]   CELL CYCLE-DEPENDENT NUCLEAR-LOCALIZATION OF EXOGENOUSLY ADDED FIBROBLAST GROWTH-FACTOR-I IN BALB/C 3T3 AND HUMAN VASCULAR ENDOTHELIAL-CELLS [J].
IMAMURA, T ;
OKA, S ;
TANAHASHI, T ;
OKITA, Y .
EXPERIMENTAL CELL RESEARCH, 1994, 215 (02) :363-372