Role of Endogenous Basic Fibroblast Growth Factor in the Healing of Gastric Ulcers in Rats

The Japanese Journal of Pharmacology

Nobuhiro Inatomi⁵  Fumihiko Sato⁵  Hiroshi Satoh⁵  Sandor Szabo⁴  Shoichi Asano⁵  Hideaki Nagaya⁵  Akio Shino¹  Izumi Murakami⁵  Koichi Kato²  Judah Folkman³ 

[1] Pharmaceutical Development Division, Takeda Chemical Industries, Ltd.;Discovery Research Division, Takeda Chemical Industries, Ltd.;Department of Surgery, Harvard Medical School;Department of Pathology, Harvard Medical School;Pharmaceutical Research Division, Takeda Chemical Industries, Ltd.

关键词: Basic fibroblast growth factor (bFGF);    bFGF mutein CS23 (TGP-580);    Angiogenesis;    Gastric ulcer;   

DOI  :  10.1254/jjp.73.59

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(40)Cited-By(22)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 × 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.

【 授权许可】

Unknown