Jpn. J. Pharmacol. 73 (1), 59-71 (1997)
Role of Endogenous Basic Fibroblast Growth Factor in the Healing of
Gastric Ulcers in Rats
Hiroshi Satoh (1), Akio Shino (2), Fumihiko Sato (1), Shoichi Asano (1),
Izumi Murakami (1), Nobuhiro Inatomi (1), Hideaki Nagaya (1), Koichi Kato
(3), Sandor Szabo (4) and Judah Folkman (5)
(1) Pharmaceutical Research Division, (2) Pharmaceutical Development
Division, (3) Discovery Research Division, Takeda Chemical Industries, Ltd.,
2-17-85 Jusohonmachi, Yodogawa-ku, Osaka 532, Japan
(4) Department of Pathology, (5) Department of Surgery, Harvard Medical
School, Boston, Massachusetts 02115, USA
Abstract: Recently, it has been pointed out that growth factors
play an important role in the healing of gastrointestinal ulcers. In the
present study, we examined the role of endogenous basic fibroblast growth
factor (bFGF) in the healing of gastric ulcers in the rat. In male SD rats,
gastric ulcers were induced in the antrum by injection of acetic acid. Time-dependent
changes in the area and bFGF content in the ulcerated area and distribution
of bFGF in the ulcerated mucosa were examined. Effects of bFGF mutein CS23
(TGP-580) and a monoclonal antibody for bFGF (MAb 3H3) on the healing of
the gastric ulcers and angiogenesis in the ulcer bed were also examined.
The content of bFGF in the ulcerated area increased with time as the ulcer
healed and reached a maximum 7 days after ulcer formation. In the gastric
ulcer bed, many cells such as fibroblasts and macrophages were positively
stained immunohistochemically by anti-bFGF antiserum. MAb 3H3 (0.1 mg/rat/day,
i.v.) inhibited angiogenesis in the ulcer bed and significantly delayed
ulcer healing, while TGP-580 (0.001 - 0.1 mg/kg x 2/day, p.o.) increased
the number of microvessels in the ulcer bed and accelerated the healing.
These results suggest that endogenous bFGF may play an important role in
the healing of gastric ulcers in the rat and that the angiogenic properties
of bFGF (TGP-580) may be involved in its effect on ulcer healing.
Keywords: Basic fibroblast growth factor (bFGF), bFGF mutein CS23 (TGP-580),
Angiogenesis, Gastric ulcer
Copyright© The Japanese Pharmacological Society 1997
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