Disease relevance of Tff1

• cDNA cloning of rat pS2 peptide and expression of trefoil peptides in acetic acid-induced colitis [1].
• The loss of pS2 expression in metaplasia and cancer supports a role for this protein in gastric tumor suppression [2].
• ITF was also induced in human intestinal metaplasia and conserved in all gastric cancers, whereas expression of the gastric peptide pS2 was progressively reduced in the progression from metaplasia to dysplasia [2].
• The apoptotic cell death induced by PS2 protein was sensitive to pertussis toxin, suggesting that heterotrimeric GTP-binding proteins are involved [3].
• CONCLUSION: The increase in the concentration of TFF1/pS2 in gastric secretions during chronic omeprazole-induced achlorhydria may be important in preventing tissue injury and promoting repair in response to an increased luminal bacterial population [4].

High impact information on Tff1

• Trefoil factor (TFF)1 is synthesized and secreted by the normal stomach mucosa and by the gastrointestinal cells of injured tissues [5].
• Distribution and metabolism of intravenously administered trefoil factor 2/porcine spasmolytic polypeptide in the rat [6].
• The rate of migration of cells at the leading edge of wounded monolayers of the human colonic cell line HT29 was increased by addition of dimeric or monomeric forms of pS2-TFF1 (0.65-325 micrograms/ml) [7].
• We found that the 4-fluoro derivatives were more estrogenic than the 4-chloro and 4-bromo derivatives as demonstrated by a higher binding affinity for estrogen receptors alpha and beta, an enhanced induction of alkaline phosphatase activity in Ishikawa cells, pS2 expression in S30 cells, and PR expression in Ishikawa cells [8].
• Members of the trefoil factor (TFF) family are mucin-associated polypeptides that are expressed along the entire length of the gastrointestinal tract [9].

Chemical compound and disease context of Tff1

• This study investigated the spatiotemporal relationship between TFF3 expression and morphological changes during intestinal damage and repair in a rat model of methotrexate-induced small intestinal mucositis [10].

Biological context of Tff1

• This adaptation to WRS was accompanied by increased GMBF (being increased by 94.2 %), active cell proliferation in the neck region of gastric glands, and increased expression of pS2 (0.37+/-0.02 vs 0.77+/-0.01, P<0.01) and ITF (0.040+/- 0.001 vs 0.372+/-0.010, P<0.01) [11].

Anatomical context of Tff1

• Additionally, the present results suggest a role for enteric nervous system and resident immune cells in mediation of colonic TFF3 secretion [12].
• TFF3 peptide, however, was depleted during histological damage and normalized during repair, mirroring the disappearance and repopulation of goblet cells [10].

Associations of Tff1 with chemical compounds

• TFF3 was barely detected in crude luminal samples [12].
• In contrast, dithiothreitol (DTT) treatment of the effluent revealed TFF3 immunoreactivity, which amounted to about 0.3 pmol min(-1) cm(-1) in the basal state [12].
• Bethanechol (10(-6)-10(-4) M), vasoactive intestinal peptide (VIP, 10(-8)-10(-7) M) or bombesin (10(-8)-10(-7) M) induced a dose-dependent release of TFF3 [12].
• After a bolus administration of 1 ml isotonic saline into the lumen, TFF3 secretion was induced by a 30-min intra-arterial infusion of the compounds to be tested [12].
• The degranulator compound bromolasalocid, 16,16-dimethyl PGE2 (dmPGE2) or interleukin-1-beta (IL-1-beta) also evoked a marked release of TFF3 [12].

Other interactions of Tff1

• Cyclooxygenase 2, pS2, inducible nitric oxide synthase and transforming growth factor alpha in gastric adaptation to stress [13].

Analytical, diagnostic and therapeutic context of Tff1

• TFF3 was evaluated in the luminal effluent using a newly developed radioimmunoassay [12].
• Gel chromatography of DTT-treated luminal samples revealed a single peak that co-eluted with the monomeric form of TFF3 [12].
• The results were demonstrated further by immunohistochemistry of pS2 (0.95+/-0.11 vs 1.41+/-0.04, P<0.01) and ITF (0.134+/-0.001 vs 0.253+/-0.01,P<0.01) [11].
• Expression of pS2 and ITF mRNA was determined by RT-PCR [11].

References