Basic fibroblast growth factor suppresses radiation-induced apoptosis and TP53 pathway in rat small intestine.
The effect of basic fibroblast growth factor (bFGF) was studied in radiation-induced apoptosis in rat jejunal crypt cells. Six-week-old male Wistar rats were administered 4 mg/kg bFGF intraperitoneally 25 h before receiving 8 Gy whole-body X rays. The jejunum was removed for analysis from time 0 to 120 h after irradiation. Villus length in control rats declined steadily until 72 h, while in bFGF-treated rats the villi were longer than in the controls until 48 h. Crypt lengths were similar to villi. bFGF treatment increased Ki-67-positive cells in the jejunal crypt at 0, 24 and 48 h. The treatment with bFGF reduced the number of apoptotic cells per jejunal crypt to 23% and 10% of the control values at 3 and 6 h, respectively, and increased numbers of mitotic cells significantly at 48 and 72 h. bFGF decreased the levels of TP53, CDKN1A, Puma and Cleaved caspase 3 at 3 h as detected by Western blot analyses. Our results suggest that bFGF protected against acute radiation-induced injury by suppressing the crypt apoptotic cells including the stem cells and promoted crypt cell proliferation. The inhibition of apoptosis thus might be related to suppression of the TP53 pathway.
Matsuu-Matsuyama
Mutsumi
M
Division of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan. mutsumi@nagasaki-u.ac.jp
Nakashima
Masahiro
M
Shichijo
Kazuko
K
Okaichi
Kumio
K
Nakayama
Toshiyuki
T
Sekine
Ichiro
I
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D016222:Fibroblast Growth Factor 2; D053148:Caspase 3