TFF2
Trefoil factor 2 precursor (Spasmolysin) (Spasmolytic polypeptide) (SP) [SML1]
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Normal circadian variations in vasoactive intestinal polypeptide, somatostatin, cholecystokinin and pancreatic polypeptide were measured to determine if these alter with aging and to identify gastrointestinal regulatory hormones that might control the dramatic diurnal variation in the gastric cytoprotective trefoil protein TFF2. Plasma pancreatic polypeptide concentrations showed a marked diurnal rhythm (p < 0.0001). Basal and postprandial pancreatic polypeptide concentrations increased with age (p < 0.01). The timing of the diurnal rhythm was consistent with pancreatic polypeptide inhibiting TFF2 secretion and there was a negative association between pancreatic polypeptide and TFF2 concentrations (p < 0.002). The much higher pancreatic polypeptide concentrations in older people will induce increased satiety that may contribute to 'anorexia of ageing'. These results identify potential therapies for treatment of gastric mucosal morbidity and age-associated loss of appetite.
MeSH Terms
- Adolescent
- Adult
- Age Factors
- Aged
- Aged, 80 and over
- Aging
- Circadian Rhythm
- Feeding Behavior
- Gastric Mucosa
- Humans
- Middle Aged
- Pancreatic Polypeptide
- Peptides
- Time Factors
- Trefoil Factor-2
To determine if the normal TFF2 diurnal rhythm is disrupted in those with increased risk of gastric morbidity. Trefoil proteins protect the gastrointestinal mucosa from damage and aid its repair. TFF2 is considered the major cytoprotective gastric trefoil protein. There is a marked circadian variation in gastric luminal TFF2 in young healthy volunteers with peak levels present during the night. Gastric juice was aspirated at two hourly intervals over a 24-h period via a nasogastric tube. TFF2 was measured by quantitative western transfer analysis. Helicobacter pylori (H. pylori) status was measured by C13 urea breath test and by serology. The effects of H. pylori infection, sleep deprivation, and ageing, which cause increased gastric morbidity, on the TFF2 circadian rhythm were tested. H. pylori infection attenuated the increase in TFF2 that occurs during the night. The TFF2 diurnal rhythm was reduced in older people and both the TFF2 level reached and the time at which the maximum TFF2 concentration occurs were associated inversely with age (p < 0.005). Sleep deprivation delayed the normal night time increase in gastric TFF2 and resulted in an overall reduction in TFF2 secretion. H. pylori infection, ageing, and sleep deprivation cause a reduction in the TFF2 diurnal rhythm. The demonstration that the TFF2 rhythm is impaired in cohorts of individuals known to suffer gastric symptoms suggests that interventions to restore the normal TFF2 rhythm in those with poor mucosal protection could reduce morbidity.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aging
- Circadian Rhythm
- Cytoprotection
- Gastric Mucosa
- Helicobacter Infections
- Helicobacter pylori
- Humans
- Middle Aged
- Mucins
- Muscle Proteins
- Peptides
- Sleep
- Trefoil Factor-2
The trefoil factors (TFF1-3) are cysteine-rich peptides expressed in the gastrointestinal tract where they play a critical role in mucosal protection and repair. The expression is up-regulated at sites of ulceration in various chronic inflammatory diseases. Recently, we presented an ELISA method for measurement of TFF3. The aims of the present study were to develop and evaluate ELISAs for the other two known human trefoil peptides, TFF1 and TFF2, and to carry out a cross-sectional study on serum TFF levels in patients with inflammatory bowel disease (IBD). The TFF1-ELISA was based on two polyclonal rabbit antibodies and the TFF2-ELISA on a monoclonal mouse antibody and a polyclonal rabbit antibody. RhTFF1 and 2 were employed to prepare the calibrators. TFF1-3 were assayed in serum from IBD patients (n=41) and controls (n=13). The TFF1- (TFF2-) ELISA had a detection limit of 3 pmol/L (6 pmol/L) and an analytical imprecision (CV(A)) of 7.0-8.8 for mean concentrations of 24-120 pmol/L (6.1-8.0 for mean concentrations of 17-77 pmol/L). The central reference intervals (n=300) were 140-1400 pmol/L (37-190 pmol/L). There was no variation with age and menstrual cycle. Food intake reduced concentrations of TFF1 by approximately 15%, but did not influence concentrations of TFF2. TFF1 and TFF3 were increased in serum from IBD patients. We have developed assays for measuring TFF1 and TFF2. Finding increased TFF concentrations in serum from IBD patients suggests that measurements of trefoil peptides may be of clinical relevance in IBD.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aging
- Enzyme-Linked Immunosorbent Assay
- Female
- Health
- Humans
- Immunoassay
- Inflammatory Bowel Diseases
- Male
- Middle Aged
- Mucins
- Muscle Proteins
- Peptides
- Proteins
- Sensitivity and Specificity
- Trefoil Factor-1
- Trefoil Factor-2
- Trefoil Factor-3
- Tumor Suppressor Proteins
The origin of gastric metaplasia of the duodenum (GMD) remains enigmatic. We studied expression of mucins and trefoil peptides in GMD to gain insight into its phenotype and origin. We examined duodenal tissue of 95 patients (0 to 83 years old, 26 with gastric Helicobacter pylori infection) for the presence of GMD. Expression was examined immunohistochemically of secretory mucins (MUC2, MUC5AC, MUC5B, and MUC6), trefoil peptides (TFF1, TFF2, and TFF3), and sucrase-isomaltase (SI). GMD, found in 37 patients, correlated positively to gastric H. pylori infection, age, and villus atrophy. MUC2 and TFF3, expressed in normal goblet cells, were absent from 100% and 87% of GMD, respectively. GMD ubiquitously expressed MUC5AC, whereas MUC5AC expression in adjacent goblet cells was closely correlated with the extent of GMD. TFF1, TFF2, and MUC6 were found in 84%, 92%, and 65% of GMD, respectively. MUC5B was absent from epithelium and GMD. SI, expressed by villus enterocytes, was absent from GMD. Brunner's glands ubiquitously expressed MUC5B, MUC6, and TFF2. GMD was characterized by the expression of gastric-type proteins MUC5AC, MUC6, TFF1, and TFF2 and the absence of intestinal markers MUC2, TFF3, and SI. In terms of the location of metaplastic cells, our results suggest that epithelial cells migrating toward villus tips switch to gastric-type secretory cells. Positive correlation with infection suggests an inductive role H. pylori in the development of GMD.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aging
- Brunner Glands
- Cell Differentiation
- Child
- Child, Preschool
- Duodenum
- Gastric Mucosa
- Goblet Cells
- Growth Substances
- Helicobacter Infections
- Helicobacter pylori
- Humans
- Infant
- Metaplasia
- Middle Aged
- Mucin 5AC
- Mucin-2
- Mucin-5B
- Mucin-6
- Mucins
- Muscle Proteins
- Neuropeptides
- Peptides
- Proteins
- Stomach Diseases
- Trefoil Factor-1
- Trefoil Factor-2
- Trefoil Factor-3
- Tumor Suppressor Proteins