Role of endogenous basic fibroblast growth factor in the healing of gastric ulcers in rats.
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.
Satoh
H
H
Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., Yodogawa-ku, Osaka, Japan.
Shino
A
A
Sato
F
F
Asano
S
S
Murakami
I
I
Inatomi
N
N
Nagaya
H
H
Kato
K
K
Szabo
S
S
Folkman
J
J
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D013270:Stomach / Q000098:blood supply / Q000187:drug effects; D013276:Stomach Ulcer / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects
D000897:Anti-Ulcer Agents; D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins; C065198:protein CS23; D005346:Fibroblast Growth Factors; D002927:Cimetidine