Therapeutic effects of rectal administration of basic fibroblast growth factor on experimental murine colitis.
OBJECTIVE
Basic fibroblast growth factor (bFGF) is a promising therapeutic agent for various diseases. It remains unclear, however, whether bFGF is effective for the treatment of inflammatory bowel disease. The aim of this study was to examine the efficacy of bFGF on 2 experimental murine colitis models and to investigate its molecular mechanisms.


METHODS
We evaluated the effects of human recombinant bFGF (hrbFGF) on mice with dextran sulfate sodium (DSS)-induced colitis and mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis as well as normal mice. Body weight, survival rate, and histologic findings of the colonic tissues were examined. Gene expression of tumor necrosis factor (TNF)-alpha, cyclooxygenase (COX)-2, transforming growth factor (TGF)-beta, mucin 2 (MUC2), intestinal trefoil factor (ITF), and vascular endothelial growth factor (VEGF) in the colonic tissues was determined. The proliferation activity of hrbFGF on the colonic epithelium was evaluated by immunohistochemistry.


RESULTS
Rectal administration of hrbFGF ameliorated DSS-induced colitis in a dose-dependent manner. Gene expression of TNF-alpha was significantly reduced in the colonic tissues of mice with DSS-induced colitis treated with hrbFGF, whereas MUC2 and ITF messenger RNA expression was up-regulated. Rectal administration of hrbFGF significantly improved the survival rate of mice with TNBS-induced colitis and partially ameliorated colitis. hrbFGF significantly increased the number of Ki-67-positive cells in the colonic epithelium of normal mice, and up-regulated the gene expression of COX-2, TGF-beta, MUC2, ITF, and VEGF in the colonic tissues.


CONCLUSIONS
Rectal administration of bFGF might be a promising option for the treatment of inflammatory bowel disease.
Matsuura
Minoru
M
Department of Gastroenterology and Endoscopic Medicine, Kyoto University, Kyoto, Japan.
Okazaki
Kazuichi
K
Nishio
Akiyoshi
A
Nakase
Hiroshi
H
Tamaki
Hiroyuki
H
Uchida
Kazushige
K
Nishi
Toshiki
T
Asada
Masanori
M
Kawasaki
Kimio
K
Fukui
Toshiro
T
Yoshizawa
Hazuki
H
Ohashi
Shinya
S
Inoue
Satoko
S
Kawanami
Chiharu
C
Hiai
Hiroshi
H
Tabata
Yasuhiko
Y
Chiba
Tsutomu
T
D000285:Administration, Rectal; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D003106:Colon / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D016019:Survival Analysis; D014302:Trinitrobenzenesulfonic Acid; D014945:Wound Healing
D016207:Cytokines; D018836:Inflammation Mediators; D019394:Ki-67 Antigen; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate