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

Abstract

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.

An Overview of Acetic Acid Ulcer Models<br>&mdash;The History and State of the Art of Peptic Ulcer Research&mdash;

“…39,40) In contrast to cortisone treatment, free perforation of ulcers was not observed with indomethacin treatment for up to 8 weeks. It is also of note that Satoh's group 41,42) discovered that indomethacin treatment for 1 week beginning 6 weeks after acetic acid ulcer induction apparently induced a relapse of healed ulcers. Histologic studies suggest that the mechanism underlying delayed ulcer healing observed with steroids and indomethacin could be partially explained by inhibited ulcer base contraction due to decreased collagen-containing connective tissue.…”

“…Satoh's group 41,42) reported a series of experiments on the relapse of healed acetic acid ulcers in rats by indomethacin treatment and prevention of such ulcer relapse by bFGF mutein (CS23). First, Satoh demonstrated that CS23 significantly enhanced ulcer healing by administering it for 4 weeks after ulceration.…”

The Role of Capsaicin-Sensitive Afferent Nerves in Gastric Mucosal Protection Initiated Centrally or Peripherally under Experimental Conditions

“…It was suggested that, the active HGF, produced in the stomach after injury, may stimulate the proliferation of gastric mucosal epithelial cells through increased number of HGF receptor. Basic fibroblast growth factor (bFGF) a potent stimulant of angiogenesis, and accelerates the healing of experimental gastric and duodenal ulcers in rats [52,53]. In ulcerated human gastric mucosa, immunoreactive bFGF is upregulated [54], thought additional data suggest that bFGF mRNA expression is an early event after mucosal injury [55].…”

Alteration of Gastric Ulcerogenic and Healing Responses in Rats With Adjuvant-Induced Arthritis

“…Several studies have shown that bFGF exerts a healing promoting effect on experimentally-induced gastric and duodenal ulcers in rats (28,29). In addition, daily administration of CS-23, a recombinant human bFGF, significantly accelerated the healing of gastric ulcers in both normal and arthritic rats, without any influence on the acid secretion or the severity of arthritis.…”