Effect of basic fibroblast growth factor on gastric ulcer healing and its own mRNA expression

Background: The application of an acid-stable mutein of basic fibroblast gr owth factor (bFGF) called CS23 results in acceleration of ulcer healing. Th e modes by which this cytokine exerts these effects are not pet completely understood. Aim: To describe the pattern of bFGF-mRNA expression during ulcer healing a nd to examine the effects of exogenously applied CS23 on gastric ulcer heal ing in an animal model. Methods: The speed of healing of gastric ulcers, expression of extracellula r matrix gene mRNAs such as pro alpha(I) collagen (by non-radioactive in si tu hybridization), cellular proliferation evidenced by the display of PCNA (by immunohistochemistry), angiogenesis, and the feedback of this growth fa ctor on its own mRNA expression pattern were used to evaluate the effects o f CS23 on rat gastric ulcer healing in an animal model. Results: CS23 accelerates gastric ulcer healing at 7, 14 and 21 days after ulcer induction. We found an increase in connective tissue beneath the ulce r bed in treated animals in comparison to controls, The expression of PCNA as well as pro alpha(I) collagen mRNA was markedly increased in ulcers, yet there was no distinct difference between treatment arms. In contrast, the density of microvessels was significantly increased in the submucosa of ulc ers by CS23 application. bFGF-mRNA expression is up-regulated in the submuc osa during early ulcer healing; this increase diminishes within days but ca n be restituted by the exogenous application of CS23. Conclusions: CS23 speeds gastric ulcer healing and significantly increases the density of microvessels in the ulcerated tissue without affecting the n umbers of proliferating cells or the transcription of collagen mRNA. In add ition, it augments the expression of bFGF-mRNA during the later stages of h ealing, suggesting a positive feedback loop.