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 growth factor (bFGF) called CS23 results in acceleration of ulcer healing. The modes by which this cytokine exerts these effects are not yet completely understood.


OBJECTIVE
To describe the pattern of bFGF-mRNA expression during ulcer healing and to examine the effects of exogenously applied CS23 on gastric ulcer healing in an animal model.


METHODS
The speed of healing of gastric ulcers, expression of extracellular matrix gene mRNAs such as pro alpha(I) collagen (by non-radioactive in situ hybridization), cellular proliferation evidenced by the display of PCNA (by immunohistochemistry), angiogenesis, and the feedback of this growth factor on its own mRNA expression pattern were used to evaluate the effects of 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 ulcer 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 ulcers by CS23 application. bFGF-mRNA expression is up-regulated in the submucosa during early ulcer healing; this increase diminishes within days but can 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 numbers of proliferating cells or the transcription of collagen mRNA. In addition, it augments the expression of bFGF-mRNA during the later stages of healing, suggesting a positive feedback loop.
Pohle
T
T
Department of Internal Medicine B, University of Münster, Münster, Germany. pohlet@uni-muenster.de
Shahin
M
M
Domschke
W
W
Konturek
J W
JW
D000818:Animals; D015415:Biomarkers; D002196:Capillaries / Q000473:pathology; D003094:Collagen / Q000096:biosynthesis; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000473:pathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors
D015415:Biomarkers; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D003094:Collagen