Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peptides of the trefoil factor family (TFF1, TFF2 and TFF3) are co-secreted with mucus in most organ systems and are believed to interact with mucins to produce high-viscosity, stable gel complexes. We have previously demonstrated that cells in the GI tract possess binding sites to TFF2 and that injected TFF2 ends up in the mucus layer. In the present study, tissue binding and metabolism of parenterally administered human TFF1 and TFF3 in rats were described and compared to the immunohistochemical localization of the TFF peptides. 125I-TFF1 monomer and 125I-TFF3 mono- and dimer were given intravenously to female Wistar rats. The tissue distribution was assessed by gamma counting of organ samples and by autoradiography of histological sections. The degradation of 125I-TFF3 was studied by means of trichloracetic acid (TCA) precipitation and the saturability of the binding by administration of excess unlabelled peptide. The TFF peptides were localized in histologic sections from the GI tract by immunohistochemistry. Injected TFF3 dimer (12%) was taken up by the GI tract. At autoradiography, grains were localized to the same cells that were immunoreactive to TFF2. The binding could be displaced by excess TFF3. Similar binding was observed for the TFF1 and TFF3 monomers apart from binding in the stomach, where the uptake was only 15% in comparison to the dimer. There was no specific binding outside the GI tract and no binding to TFF1 or TFF3 immunoreactive cells. In conclusion, the TFF2-binding cells in the gastrointestinal tract seem to have basolateral, receptor-like activity to all three TFF peptides. The mucous neck cells of the stomach predominantly take up TFFs with two trefoil domains, indicating a different receptor-like activity in the stomach compared to the rest of the GI tract.
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PMID:Injected TFF1 and TFF3 bind to TFF2-immunoreactive cells in the gastrointestinal tract in rats. 1297 24

The trefoil protein TFF3 forms a homodimer (via a disulfide linkage) that is thought to have increased biological activity over the monomer. The solution structure of the TFF3 dimer has been determined by NMR and compared with the structure of the TFF3 monomer and with other trefoil dimer structures (TFF1 and TFF2). The most significant structural differences between the trefoil domain in the monomer and dimer TFF3 are in the orientations of the N-terminal 3(10)-helix (residues 10-12) and in the presence in the dimer of an additional 3(10)-helix (residues 53-55) outside of the core region. The TFF3 dimer forms a more compact structure as compared with the TFF1 dimer where the two trefoil domains are connected by a flexible region with the monomer units being at variable distances from each other and in many different orientations. Although TFF2 is also a compact structure, the dispositions of its monomer units are very different from those of TFF3. The structural differences between the dimers result in the two putative receptor/ligand binding sites that remain solvent exposed in the dimeric structures having very different dispositions in the different dimers. Such differences have significant implications for the mechanism of action and functional specificity for the TFF class of proteins.
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PMID:Solution structure of the disulfide-linked dimer of human intestinal trefoil factor (TFF3): the intermolecular orientation and interactions are markedly different from those of other dimeric trefoil proteins. 1469 Apr 24

TFF3 is a member of the trefoil factor family (TFF) peptides, which enhance the surface integrity of mucous epithelia, and is typically secreted by intestinal goblet cells together with the mucin MUC2. Reports of the expression of TFF3 within the normal human stomach are contradictory and the precise localisation of TFF3 is unknown. We have mapped the human gastric mucosa by reverse transcription/polymerase chain reaction and Western blot analysis and by immunohistochemistry. Small amounts of TFF3 were detectable in the oxyntic mucosa of the corpus, whereas TFF3 synthesis increased sharply distal to the corpus-antrum transitional zone. TFF3 secretion was demonstrated in the antrum, the pyloric region and the proximal duodenum. High TFF1 levels were present in all regions of the gastric mucosa including the corpus, whereas the proximal duodenum was nearly devoid of TFF1. Immunohistochemistry localised TFF3 to antral and pyloric surface mucous cells. In the antrum, an increasing concentration gradient was found towards cells deeper in the isthmus. TFF1 was confined to superficial pit cells in the antrum. TFF3 was also present in specific layers of the laminated mucous gel of the antral and pyloric regions and variable concentrations of TFF3 (2-62 nmol/l) were measured in gastric juice. Here, a probably N-terminally shortened variant is present that forms disulphide-linked dimers. Thus, TFF3 is a typical secretory peptide of the normal human antral and pyloric gastric mucosa and has a gastric expression pattern different from that of TFF1 and TFF2. TFF3 might therefore have important physiological functions in the stomach, e.g. as a luminal surveillance peptide maintaining particularly the integrity of the antral and pyloric mucosa.
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PMID:A gradient of TFF3 (trefoil factor family 3) peptide synthesis within the normal human gastric mucosa. 1496 59

The expression of the trefoil factor family (TFF) genes (TFF1, TFF2, and TFF3) was systematically analyzed in 18 different organs from male or female mice using RT-PCR analysis. The expression patterns showed some gender-specific differences, e.g., TFF3 transcripts in the urinary bladder and liver. Furthermore, the murine expression profile differed from that in human, e.g., in the respiratory tract and uterine cervix. As a hallmark, an aberrant TFF1-related transcript was detected specifically in the kidney and liver of several mouse strains. Molecular characterization of this rare 1.8kb long transcript from the kidney clearly revealed that its 3' region originated from the antisense strand of the TFF1 locus containing particularly large parts of the antisense strands of introns 1 and 2. Homology searches using various databases revealed that this antisense TFF1-related transcript is subject of intense alternative splicing and no protein product encoded by this antisense TFF1-related transcript could be identified. Although the function of this transcript is not known currently, we can speculate that this antisense TFF1-related transcript might have a gene silencing effect particularly on TFF1 expression in the murine kidney and liver.
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PMID:Profiling trefoil factor family (TFF) expression in the mouse: identification of an antisense TFF1-related transcript in the kidney and liver. 1517 69

Trefoil factor family (TFF) 1, 2, and 3 is a mucin-associated protein involved in the maintenance of mucosal barrier and restitution of lining epithelial cells. In this study, the expression of TFF1, 2, and 3 and MUC mucins were examined immunohistochemically in hepatolithiasis and control livers. The expression of TFF1, 2, and 3 were augmented markedly in biliary mucosa in hepatolithiasis in coordinate with gel-forming mucin. TFF3 was detected in hepatic bile samples of hepatolithiasis. Augmented expression and secretion of TFF in biliary mucosa in hepatolithiasis may play a role in lithogenesis together with gel-forming mucin in addition to mucosal defense and repair.
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PMID:Expression of trefoil factor family 1, 2, and 3 peptide is augmented in hepatolithiasis. 1517 70

At the gastric cardia, the molecular mechanisms of inflammation and metaplasia are incompletely understood. Thus, the aim of this study was to determine the expression of TFF1, TFF2 and TFF3 at this site and correlate these data with Helicobacter pylori infection or gastro-esophageal reflux disease (GERD). In 27 patients without intestinal metaplasia at the cardia, endoscopic biopsies were obtained for histology and RT-PCR. TFF1 and TFF2 were expressed in all cardia samples. TFF3 expression was significantly more frequent at the cardia (n = 15/24) than in the corpus (n = 2/26). TFF3 expression at the cardia was mainly observed in GERD patients, and there was a clear tendency towards higher interleukin-8 (IL-8) transcription levels; whereas TFF3 expression was not correlated with the H. pylori status or to tumor necrosis factor-alpha (TNF-alpha) expression. The expression of TFF3 at the cardia may represent an adaptation to GERD and precede the development of Barrett's esophagus.
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PMID:TFF3 expression at the esophagogastric junction is increased in gastro-esophageal reflux disease (GERD). 1517 71

We studied the expression of trefoil peptides in the different types of intestinal metaplasia of the stomach. Endoscopic biopsy was performed in 132 patients with dyspepsia. Intestinal metaplasia subtype was classified according to the pattern of alcian blue/PAS staining and high iron diamine staining. Expression of trefoil peptides was measured by immunohistochemistry. TFF1 and TFF3 were mainly expressed in goblet cells and TFF2 in columnar cells in all the types of intestinal metaplasia. There was a gradual decrease of TFF1 and TFF3, and increase of TFF2, during the progression of intestinal metaplasia from type I to type III via the type II intermediate.
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PMID:Expression of trefoil peptides in the subtypes of intestinal metaplasia. 1517 72

TFF peptides (formerly P domain peptides, trefoil factors) are typical secretory products of mucin-producing cells and are thought to influence the rheological properties of mucous gels. We investigated the localization of these peptides in the human false vocal folds of the larynx, also known as the ventricular folds or vestibular folds. An analysis of TFF peptide mRNA by RT-PCR and TFF protein by Western blot detected TFF1 and TFF3, but not TFF2. Immunohistochemistry revealed TFF1 to be associated with the secretory product of goblet cells and mucous parts of subepithelial seromucous glands. TFF3 occurred in columnar epithelial cells of the mucosa and in serous cells and excretory duct cells of seromucous glands. These peptides may play a role in the rheological function of mucus secreted onto the true vocal folds and are thus important constituents of vocal production.
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PMID:TFF peptides in the human false vocal folds of the larynx. 1517 76

The central cornea of 10 cadavers and 33 patients suffering from keratoconus, herpetic keratitis, Fuchs' dystrophy and pterygium were analysed focusing on the expression of TFF peptides by means of reverse transcription polymerase chain reaction and immunohistochemistry. TFF1 and TFF3 transcripts were detected in healthy corneae as well as in pterygia. Only TFF3 mRNA was transcribed in keratoconus, Fuchs' dystrophy and herpetic keratitis. Immunohistochemistry revealed absence of all three TFF peptides in healthy corneae but production of TFF3 in each of the diseased corneae. In pterygia both TFF1 and TFF3 synthesis was detectable in goblet cells. The absence of TFF peptide production in the healthy cornea indicates that TFF3 secretion is induced in different corneal diseases by yet unknown stimuli. Here TFF3 synthesis can be interpreted as a protection mechanism, because all corneal diseases analysed are characterized by progressive tissue destruction. TFF1 and TFF3 production by goblet cells in pterygia is comparable to the healthy conjunctiva suggesting that TFF peptides do not play a significant role in the pathogenesis of pterygia.
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PMID:Distribution of TFF peptides in corneal disease and pterygium. 1517 77

Trefoil factor family (TFF) peptides, besides their prominent expression in mucous epithelia, are also synthesized in the central nervous system. Previously TFF1 expression was observed in mouse brain astrocytes, while oxytocinergic neurons of the hypothalamo-pituitary axis are recognized sites of TFF3 synthesis. Here, the expression of TFF1, TFF2, and TFF3 was systematically studied using reverse transcription-polymerase chain reaction (RT-PCR) analysis of dissected adult mouse brain regions including the pituitary. Additionally, the developmental profile of TFF expression in murine cerebral cortex and cerebellum was monitored. Overall, the expression patterns of the three TFF genes differed. The TFF1 and TFF2 profiles shared some similarities, whereas the TFF3 expression pattern was completely different. TFF1 was nearly uniformly, but weakly expressed in all brain regions tested. The TFF1 and TFF2 expression patterns differed characteristically in the pituitary where abundant TFF2 transcription was detected in the anterior and not the posterior lobe and the expression level in males was higher than in females. In contrast, TFF3 expression was limited to the hippocampus, the temporal cortex, and the cerebellum, the latter being surprisingly the major site of expression. Here, TFF3 mRNA appeared to be restricted mainly to neurons and not glial cells. Cerebellar TFF3 expression is clearly developmentally regulated (maximum at P15), indicating a role for TFF3 during postnatal cerebellar development.
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PMID:Trefoil factor family (TFF) expression in the mouse brain and pituitary: changes in the developing cerebellum. 1517 78


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