Expression of trefoil peptides pS2 and human spasmolytic polypeptide in gastric metaplasia at the margin of duodenal ulcers.

Abstract

Duodenal ulcers are associated with gastric metaplasia in the duodenum, both at the ulcer margin and at more distant sites in the duodenal bulb. pS2 and human spasmolytic polypeptide (hSP) are secretory peptides expressed in gastric epithelial ceils and in gastric metaplasia. As these peptides may be important in ulcer healing, this study investigated the possibility that the expression ofpS2 and hSP is increased in gastric metaplasia at the margin ofduodenal ulcers. (SEM), 20.6 (3.3) v 9.5 (3.0); p<0.001). There was a trend towards greater hSP staining at the ulcer margin but this did not achieve statistical significance. These findings support the putative role of pS2 and possible hSP in mucosal healing and providy further evidence for an autocrine 'ulcer-gastric metaplasia-repair' loop involving these trefoil peptides.

Trefoil peptide expression and goblet cell number in rat intestine: effects of KGF and fasting-refeeding

“…However, we show for the first time that KGF upregulates TFF2 expression in rat proximal small bowel, with ectopic expression in goblet cells and secretion of the peptide into the lumen. Ectopic local upregulation of TFF2 was previously shown to occur in ulcer-associated cell lineages and in goblet cells at sites of gut mucosal injury (20,25,33,46), suggesting a role for TFF2 in bowel mucosal restitution. Local KGF mRNA in gut mucosa is upregulated at sites of injury in inflammatory bowel disease and with mucosal ulceration (4,48).…”

“…In vitro and in vivo studies strongly link trefoil peptides with gastrointestinal mucosal restitution (7,19,28,41). TFF1, TFF2, and TFF3 are upregulated at sites of gastric and intestinal mucosal injury, where these proteins stimulate gut epithelial cell migration and mucosal repair (16,20,25,33,45,46). However, the role of TFF peptides in physiological and adaptive gut epithelial cell proliferation, apoptosis, and turnover remains uncertain (17,28,31,38,45).…”

Munc18/SNARE proteins’ regulation of exocytosis in guinea pig duodenal Brunner’s gland acini

“…Unfortunately, immunofluorescence studies we had carried out with a battery of antibodies directed against rat sequences (Munc18b, Syntaxin-2 and -3, VAMP-2 and -8) could not detect these proteins in the guinea pig Brunner's gland acini. Whether other secretory products (immunoglobulin, lysozyme, growth factors, trefoil peptides) of Brunner's gland acini [3][4][5] are contained in the same mucin vesicles or distinct vesicle populations involving distinct sets of exocytotic proteins is particularly intriguing and would require further investigation. …”

“…The Brunner's glands in the duodenum contribute to the discharge of mucin [1,2] and also the secretion of a number of other products, including immunoglobulin, lysozyme, epidermal growth factor, and trefoil peptides, which collectively contribute to mucosal protection [2][3][4][5] . Brunner's glands also secrete bicarbonate that contributes to the neutralization of the massive amount of acid coming from the stomach [2] , and duodenal alkalinization is critical for pancreatic enzyme survival.…”

Modulation of Epithelial Cell Adhesion in Gastrointestinal Homeostasis

“…70,71 The trefoil peptides are ectopically overexpressed in a number of human cancers 65 and within gastrointestinal mucosa affected by chronic ulcerative and inflammatory lesions such as in Crohn's disease, ulcerative colitis, and gastroduodenal peptic ulceration, suggesting a role in mucosal healing and regeneration. [72][73][74][75] They have also been found in the ulcer-associated cell lineage. 65,70 In vivo, both TFF2 and TFF3 provide sufficient protection and reduce the extent and severity of ethanol-and indomethacin-induced acute gastric injury in rats.…”