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)

Trefoil factor family (TFF)-domain peptides (formerly P-domain peptides, trefoil factors) represent major mucin-associated peptides of the gastrointestinal tract. Here, the first localization studies on TFF3 in the lower respiratory tract of human material are presented. Immunohistochemistry revealed significant accumulation of TFF3 to mucous cells in the acini of submucosal glands and varying amounts in goblet cells at the ductular portions and the surface epithelium. TFF3 appears also as a component of the mucus, for example from patients with chronic bronchitis. Expression of TFF3 was also shown by use of the polymerase chain reaction. In contrast, TFF1 and TFF2 transcripts were hardly detectable in the human respiratory tract. Thus, a structural function of TFF3 for the airway mucus is discussed, possibly together with the mucins MUC5B and MUC5AC.
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PMID:Localization of TFF3, a new mucus-associated peptide of the human respiratory tract. 1019 85

The expression of two trefoil peptides (TFF1 and TFF2) and four mucins (MUC1, MUC2, MUC5AC, and MUC6) was evaluated by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) in 29 gastric polyps, 10 hyperplastic and 19 adenomatous, eight of which displayed malignant transformation. The aims of this study were to characterize the expression profile of these molecules in each type of polyp and to investigate possible modifications of the profile during the process of malignant transformation. All hyperplastic polyps displayed immunoreactivity for TFF1, MUC5AC, and MUC1 in more than 75 per cent of the cells. In adenomatous polyps, three main phenotypes could be identified: complete gastric phenotype (co-expression of TFF1 and MUC5AC)-nine cases (47.4 per cent); incomplete gastric phenotype (TFF1-positive and MUC5AC-negative)-seven cases (36.8 per cent); non-gastric (intestinal) phenotype (no expression of TFF1 or MUC5AC)-three cases (15.8 per cent). Data yielded by immunohistochemistry and RT-PCR showed a good correlation for both TFF1 and TFF2. One hyperplastic and seven adenomatous polyps with villous architecture displayed foci of diffuse and intestinal-type carcinoma, respectively; in all of these cases, MUC1 expression and signs of gastric differentiation were observed in both the non-malignant and the carcinomatous component. It is concluded that gastric differentiation is a feature of hyperplastic polyps and of a subset of adenomatous polyps which is shared by early carcinomas arising in some of these polyps, regardless of the histological type of polyp and of carcinoma.
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PMID:Patterns of expression of trefoil peptides and mucins in gastric polyps with and without malignant transformation. 1039 19

The expression of trefoil peptides (TFF1 and TFF2) and mucins (MUC1, MUC2, MUC5AC, and MUC6) has previously been described in gastric polyps. In the present study, the expression profile of these trefoil peptides and mucins was characterized in 96 gastric carcinomas, in an attempt to further the understanding of the histogenesis and cell differentiation of gastric carcinoma. Taking together the co-expression of trefoil peptides and mucins, three phenotypes were defined: complete gastric, incomplete gastric, and non-gastric phenotype. Gastric differentiation (complete and incomplete) was observed in 30 out of 33 (90.9%) diffuse carcinomas and in 38 out of 53 (71.7%) intestinal carcinomas. Non-gastric differentiation was observed in only three (9.1%) diffuse carcinomas and in 15 (28.3%) intestinal carcinomas. The phenotypes observed in intestinal carcinomas were similar to those previously observed in adenomatous polyps, whereas most diffuse carcinomas mimicked the phenotype of hyperplastic polyps. The percentage of cases displaying a non-gastric phenotype was higher, though not significantly, in tumours that had invaded the gastric wall than in T1 tumours, regardless of histotype. It is concluded that gastric-type differentiation is retained in the majority of gastric carcinomas, being more prominent in diffuse than in intestinal carcinomas, and in early than in advanced carcinomas.
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PMID:Gastric carcinoma exhibits distinct types of cell differentiation: an immunohistochemical study of trefoil peptides (TFF1 and TFF2) and mucins (MUC1, MUC2, MUC5AC, and MUC6). 1069 92

Trefoil factor family (TFF) peptides are typical secretory products of mucin-producing cells, e.g. of the gastrointestinal tract. Here, the expression and secretion of mucins and TFF peptides was studied in the HT-29 cell line throughout cellular growth and differentiation in relation to a mucin-secreting (HT-29 MTX) or an enterocyte-like (HT-29 G(-)) phenotype. mRNAs of several MUC and TFF genes were expressed in both cell subpopulations. However, for most MUC and TFF genes, the expression appeared strongly induced with the differentiation into the mucin-secreting phenotype. On the other hand, TFF2 was specifically expressed in the mucin-secreting HT-29 MTX cells. The differentiation of HT-29 MTX cells into the mucin-secreting phenotype was characterised by secretion of the gel-forming mucins MUC2, MUC5AC, and MUC5B, however, according to a different pattern in the course of differentiation. A significant amount of TFF1 and TFF3 was secreted after differentiation, also according to a different pattern, whereas TFF2 was only faintly detected. Secretagogues, known to induce the secretion of mucus, increased the secretion of all three TFF peptides. In contrast, neither a secretory mucin nor a TFF peptide was found in the culture medium of HT-29 G(-) cells. Overlay assays indicated that HT-29 MTX mucins bound to secretory peptides of HT-29 MTX cells with relative molecular mass similar to TFF peptides. TFF1 and TFF3 were specifically localised in the mucus layer of HT-29 MTX cells by confocal microscopy. Finally, the secretion of TFF peptides and mucins appears as a co-ordinated process which only occurs after differentiation into goblet cell-like phenotype.
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PMID:Specific secretion of gel-forming mucins and TFF peptides in HT-29 cells of mucin-secreting phenotype. 1138 69

The molecular architecture of the human ocular mucus is not yet completely understood. Recently, TFF peptides (formerly known as trefoil factors or P-domain peptides) could be identified as new constituents of this delicate mucus. Members of the TFF-peptide family are typical secretory products of mucous epithelia and three are known in humans and designated as TFF1, TFF2 and TFF3. They enhance cell migratory processes (motogenic effect), they show anti-apoptotic effects and are inflammatory modulators Both TFF1 and TFF3 expression could be monitored by the reverse transcription-polymerase chain reaction (RT-PCR) in the human conjunctiva; in contrast, TFF2 transcripts were not detectable. Using immunohistochemistry, TFF1 and TFF3 peptides were found in varying concentrations solely in secretory vesicles of conjunctival goblet cells. This localisation matches precisely that of the secretory mucin MUC5AC. Thus, conjunctival TFF1 and TFF3 have to be considered as typical mucin-associated peptides probably modulating the rheological properties of the ocular mucus and the tear fluid. Future investigations are in progress to elucidate the role of TFF-peptides during pathological conditions of the eye as well as their diagnostic and therapeutic potential.
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PMID:[TFF peptides. New mucus-associated secretory products of the conjunctiva]. 1169 22

Barrett's esophagus (BE) consists of metaplastic epithelium of the esophagus, generally diagnosed by mucin histochemistry. We aimed to determine which mucins were expressed in BE, and to relate their expression to BE pathology. Archival biopsies of 4 patient groups were selected, based on standard histochemistry: BE without inflammation, BE with inflammation, ulcerating BE, and BE with dysplasia. Sections were stained by immunohistochemistry for secretory mucins (MUC2, MUC5AC, MUC5B, and MUC6), the proliferation marker Ki-67, and mucin-associated trefoil factor family (TFF) peptides (TFF1, TFF2, and TFF3). MUC5AC and TFF2 were expressed at similar high levels in each clinical group. Intestinal metaplasia (IM), detected both histochemically and by the intestinal mucin MUC2, was lowest in inflamed BE. The expression of the intestinal-type TFF3 did not differ among the groups. Ulcerating BE was distinguished by very low expression of MUC6 and MUC5B, but very high expression of TFF1. Proliferation was not different among the groups. In the total group of BE patients, H. pylori infection of the stomach correlated with decreased TFF2 expression in the BE epithelium. We conclude that BE is best characterized by the specific expression of the gastric-type markers, MUC5AC, MUC6, TFF1, and TFF2. Ulcerating BE constitutes the most distinguished group with respect to mucin and TFF expression. Of the intestinal markers, MUC2 is very specific for IM in BE, whereas TFF3 is not a marker for IM. The low occurrence of IM in inflamed BE suggests that these patients may have the lowest risk of developing carcinoma.
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PMID:Barrett's esophagus is characterized by expression of gastric-type mucins (MUC5AC, MUC6) and TFF peptides (TFF1 and TFF2), but the risk of carcinoma development may be indicated by the intestinal-type mucin, MUC2. 1215 67

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.
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PMID:Metaplasia of the duodenum shows a Helicobacter pylori-correlated differentiation into gastric-type protein expression. 1261 84

Duodenal carcinomas, such as ampullary tumors, may be a heterogeneous group of neoplasms that share differentiation features with gastric or colorectal carcinomas. Because of the cell- and tissue-specific expression patterns of mucins and trefoil peptides, these markers were used to investigate the differentiation status of duodenal and ampullary carcinomas in comparison with gastric and colorectal carcinomas. Adenocarcinomas (14 duodenal, 10 gastric, 11 ampullary and 10 colorectal) were examined immunohistochemically for the mucin gene products MUC1, MUC2, MUC5AC, MUC6 and the trefoil peptides TFF1 and TFF2. The tumors' expression profile for MUC5AC, MUC6 and TFF1 was used to distinguish between gastric- and intestinal-directed differentiation. The mucins that were most often expressed in the individual tumor types were MUC1 (duodenal and ampullary carcinomas), MUC2 (colorectal carcinomas) and MUC5AC (gastric carcinomas). Further classification focusing on the expression profile for MUC5AC, MUC6 and TFF1 revealed that 21% of the duodenal and 45% of the ampullary carcinomas demonstrated mainly gastric differentiation (positivity for all three markers or only two of them). The remaining duodenal and ampullary carcinomas showed nongastric, i.e., intestinal differentiation (all three markers negative or only one marker positive). The gastric differentiation pattern characterized 60% of gastric carcinomas. Colorectal carcinomas showed intestinal differentiation in 100% of cases. Duodenal carcinomas have a heterogeneous mucin expression pattern that is mainly related to either gastric differentiation or intestinal differentiation. This also holds for ampullary carcinomas. Among the markers used, MUC5AC, MUC6 and TFF1 are most useful for revealing differentiation pathways in duodenal and ampullary carcinoma.
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PMID:Differentiation pathways in duodenal and ampullary carcinomas: a comparative study on mucin and trefoil peptide expression, including gastric and colon carcinomas. 1507 39

Why Helicobacter pylori colonizes only gastric tissue is unknown. It is found on gastric mucus-secreting cells and in the overlying gastric mucus but not deep in gastric glands. This localization mirrors the expression of trefoil factor 1, TFF1. We hypothesized that H. pylori interacting with TFF1 could explain the tropism of this bacteria for gastric tissue. Recombinant human TFF1 expressed in Escherichia coli was purified by affinity chromatography, ion-exchange chromatography, and gel filtration. Binding of H. pylori was assessed by using flow cytometry and the BIAcore system, which allows real-time monitoring of molecular interactions. In flow cytometry, H. pylori bound to the TFF1 dimer, but Campylobacter jejuni strains and the laboratory strain of E. coli, HB101, did not bind. When the BIAcore system was used, H. pylori bound strongly to TFF1-coated dextran chips compared with uncoated chips. Binding was inhibited by a TFF1 monoclonal antibody and by soluble TFF1. H. pylori bound to porcine gastric mucin only if it was pretreated with TFF1. In conclusion, H. pylori interacts avidly with the dimeric form of TFF1, and this interaction enables binding to gastric mucin, suggesting that TFF1 may act as a receptor for the organism in vivo. This interaction may underline the previously unexplained tropism of this organism for gastric tissue and its colocalization with the gastric mucin MUC5AC.
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PMID:Helicobacter pylori interacts with the human single-domain trefoil protein TFF1. 1512 8

The trefoil protein TFF1 is expressed principally in the superficial cells of the gastric mucosa. It is a small protein and forms homo- and hetero-dimers via a disulphide bond through Cys58 which is located three amino acids from the C terminus. TFF1 is co-expressed with the secreted mucin MUC5AC in superficial cells of the gastric mucosa suggesting that it could be involved in the packaging or function of gastric mucus. We have previously shown that TFF1 co-sediments with mucin glycoproteins on caesium chloride gradients. To extend this observation we have now used gel filtration under physiological conditions, immunoprecipitation and Western transfer analysis to characterise the interaction of TFF1 with gastric mucin glycoproteins. We show that TFF1 co-elutes with MUC5AC but not MUC6 on gel filtration and that immunoprecipitation and Western transfer analysis confirms that TFF1 interacts with MUC5AC. We also demonstrate that the TFF1 dimer is the predominant molecular form bound to MUC5AC. Salt and chelators of divalent cations such as EDTA and EGTA disrupted the TFF1- MUC5AC interaction and increased the degradation of MUC5AC, whereas calcium increased the amount of TFF1 bound to MUC5AC. These data support the contention that TFF1 is pivotal in the packaging and function of human gastric mucosa.
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PMID:The trefoil protein TFF1 is bound to MUC5AC in human gastric mucosa. 1528 36


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