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

Members of the trefoil factor (TFF) family are highly expressed in endodermal ulcerative wound healing and selectively in neoplastic proliferation of various glandular epithelia. There is some evidence that TFF1 and TFF3 affect cell motility, are indirectly involved in growth suppression, and are associated with mucin expression. TFF2 is co-expressed with TFF1 in gastric surface epithelial cells, but its potential role in vivo is unclear. We analyzed potential effects on cell proliferation and morphogenesis of TFF2 on a panel of epithelial and mesenchymal cell lines. TFF2 had no measurable effect on the proliferation of any of the cell lines tested. In type 1 collagen lattices, TFF2 at a low concentration (25-100 nM) induced the formation of highly complex branched structures in the breast carcinoma cell line MCF-7 over a period of 14 to 42 days. No significant effect was shown with other cell lines. This morphogenic effect was abolished by monoclonal antibodies specific for either TFF2 or TFF1. TFF2 did not affect cell motility in MCF-7 cells as measured by videomicroscopy, in contrast to previous studies using TFF1. TFF2-treated MCF-7 colonies showed a 30% reduction in the number of apoptotic bodies, corroborated by trypan blue exclusion and DNA fragmentation ELISA, indicating TFF2 promotes cell survival via inhibition of apoptosis and can act as a morphogen in the presence of TFF1. These properties may complement the actions of TFF1 as a motogen and may explain differential expression in endodermal wound healing.
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PMID:Trefoil factor-2, human spasmolytic polypeptide, promotes branching morphogenesis in MCF-7 cells. 1033 65

TFF-peptides (formerly P-domain peptides, trefoil factors) are typical secretory products of mucin-producing cells and seem to influence the rheological properties of mucous gels. Here, localization studies of TFF-peptides in human salivary glands are presented. Expression studies (polymerase chain reaction) revealed mainly TFF3 transcripts in submandibular and sublingual glands and trace amounts in parotid glands. Only low levels of expression of TFF1 could be monitored in submandibular and sublingual glands, and TFF2 transcripts were hardly detectable in all three major salivary glands. This result was partly confirmed by Western blot analysis, which only detected TFF3 in submandibular glands, but not in sublingual and parotid glands. TFF3 was also shown to be a constituent of human saliva. Immunofluorescence localized TFF3 solely in the secretory granules of serous cells of submandibular glands but not in mucous cells. This localization is remarkably similar to that of the unique low-molecular-weight mucin MUC7, which interacts with a number of oral microorganisms.
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PMID:Secretion of TFF-peptides by human salivary glands. 1055 50

Trefoil factor family domain peptides (TFF) are thought to be involved in mucosal epithelial restitution and wound healing of the gastrointestinal tract and are up-regulated in ulceration and in a variety of solid tumours. It was hypothesized that TFFs are also expressed on mucosal surfaces of the human respiratory tract. Lung tissue, nasal polyps, and sputum samples from seven patients with cystic fibrosis (CF), two with chronic and acute bronchitis, and non-dysplastic material from two cases of bronchial adenocarcinoma were analysed for TFF expression by immunohistochemistry, immunofluorescence, western blot and RT-PCR. Expression of TFF1 and TFF3 was observed in material from all patients. TFFs were localized in goblet and ciliated cells, as well as in some submucosal cells of tracheobronchial tissues and nasal polyps from normal and CF individuals. In sputa of patients with CF and with chronic or acute bronchitis, TFF1 and TFF3 were detected by western blotting. Freshly cultivated nasal epithelial cells transcribed and secreted TFFs and mucins, whereas nasal cells cultivated for 6 weeks still expressed mucins, but not TFFs. Secreted TFFs and mucins also bound to the surface of Staphylococcus aureus in infected CF airways. In conclusion, TFF1 and TFF3 are expressed and secreted in normal and inflamed airways. The association of TFFs with bacteria may contribute to the anti-microbial mucociliary defence system.
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PMID:Trefoil factor family domain peptides in the human respiratory tract. 1065 10

One of the early events in inflammation and epithelial restitution of the gastrointestinal tract is the up-regulation of secretory peptides belonging to the trefoil factor family (TFF) that promote cell migration, protect and heal the mucosa. Their major expression site is stomach (TFF1, TFF2) and intestine (TFF3). Located in the 5'-flanking region of the genes are several consensus sites for members of the GATA transcription factors known to control gut-specific gene expression. By reverse transcription-PCR (RT-PCR), GATA-6 was shown to be expressed in a variety of tumor cell lines of gastric, intestinal and pancreatic origin. In MKN45, KATOIII and LS174T, cotransfection with TFF reporter genes and GATA-6 expression vectors revealed that GATA-6 activates TFF1 and TFF2 4-6-fold, without an effect on TFF3. The functional contribution of GATA binding sequences in the reverse orientation was further characterized by reporter gene assays using TFF2 deletion constructs and by gel shift experiments.
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PMID:Transcription factor GATA-6 activates expression of gastroprotective trefoil genes TFF1 and TFF2. 1068 77

Trefoil factors are wound-healing peptides important in protection and healing of the human gastrointestinal tract. Their potential for therapy of gastrointestinal ulcers has been established. This study investigated the hypothesis that trefoil factors are also present in human salivary gland. Tissues from surgical biopsy specimens were collected fresh into ice and stored in liquid nitrogen. Breast, stomach, and colon constituted positive controls. Trefoil factor mRNAs were detected by reverse transcription polymerase chain reaction (RT-PCR) or by in situ hybridization (ISH) with formalin-fixed, paraffin-embedded sections. Amplified DNA fragments were ligated into pGEM-T Easy vector and used to transform competent Escherichia coli JM109, allowing sequencing to confirm identity of cloned fragments. Generation of amplifiable cDNA was confirmed using primers specific to the ubiquitously expressed abl gene. By RT-PCR, TFF1 (pS2) mRNA was detected in 14 of 15 glands, TFF3 (hITF) mRNA in 13, and TFF2 (hSP) in only 1 gland. ISH of 15 glands (7 of which had been studied by RT-PCR) showed the same pattern of expression and indicated that TFF1 mRNA was usually expressed at low levels by a few mucous cells, whereas TFF3 was produced abundantly by most mucous cells. There was no difference in patterns of expression comparing parotid, submandibular, and minor mucous glands. Nor was there an obvious relationship between trefoil factor expression and pathology, but those glands not expressing TFF1 or TFF3 had evidence of chronic inflammation or atrophy. Trefoil factors are likely to be important in healing, predisposition to, and therapy of, oral diseases.
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PMID:Trefoil factor expression in normal and diseased human salivary glands. 1082

Mammalian trefoil factors (TFFs) constitute a group of three peptides (TFF1, TFF2 and TFF3) widely distributed in the gastrointestinal tract. Although a mucosal protection/healing effect of these peptides is well documented the mechanism of action is still unknown. A mucosal membrane extract was prepared from porcine stomach scrapings and incubated with a gel containing immobilized porcine TFF2. The affinity gel material was specifically eluted with a neutral buffer containing a high concentration of the ligand (porcine TFF2). A subsequent SDS-gel electrophoresis showed one protein with a MW of approximately 220 kDa and three proteins with MW around 140 kDa. The proteins were analyzed by trypsin digestion followed by mass spectrometric sequencing of tryptic fragments. In this way a 140-kDa beta subunit of fibronectin receptor and a 224-kDa CRP-Ductin gene product were identified. The CRP-Ductin gene product (also named MUCLIN), which is expressed in the intestinal crypts, is characterized by being a membrane protein with a short cytoplasmic region, a transmembrane domain and a large extracellular region. This protein thus fulfils some of the criteria for being a TFF receptor or a TFF binding protein.
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PMID:Isolation and characterization of putative trefoil peptide receptors. 1082 94

TFF-peptides (formerly P domain peptides, trefoil factors) are typical secretory products of many mucous epithelial cells. TFF3 is also synthesized in the hypothalamus and has anxiolytic or anxiogenic activities when injected into the rat amygdala. Here we show by immunohistochemistry that TFF3 is localized to a distinct population of neurons of the human hypothalamic paraventricular and supraoptic nuclei. Generally, TFF3-positive cells are co-localized in oxytocin-producing cells and not in vasopressin-producing cells. Relatively large amounts of TFF3-but not TFF1 and TFF2-are present in the posterior lobe of the human pituitary, where it is probably released into the bloodstream. Furthermore, TFF3 was also detectable in human postmortem cerebrospinal fluid.
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PMID:Co-localization of TFF3 peptide and oxytocin in the human hypothalamus. 1083 34

An autosomal recessive nonsyndromic deafness locus, DFNB10, was previously localized to a 12-cM region near the telomere of chromosome 21 (21q22.3). This locus was discovered in a large, consanguineous Palestinian family. We have identified and ordered a total of 50 polymorphic microsatellite markers in 21q22.3, comprising 16 published and 34 new markers, precisely mapped and ordered on BAC/cosmid contigs. Using these microsatellite markers, the locus for DFNB10 has been refined to an area of less than 1 Mb between markers 1016E7.CA60 and 1151C12.GT45. Six previously published cDNAs were mapped to this critical region, and their genomic structures were determined to facilitate mutation analysis in DFNB10. All six genes in this region (in order from centromere to telomere: White/ABCG1, TFF3, TFF2, TFF1, PDE9A, and NDUVF3) have been screened and eliminated as candidates for DFNB10. The new microsatellite markers and single nucleotide polymorphisms identified in this study should enable the refined mapping of other genetic diseases that map to 21q22.3. In addition, the critical region for DFNB10 has been reduced to a size amenable to an intensive positional cloning effort.
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PMID:Refined localization of autosomal recessive nonsyndromic deafness DFNB10 locus using 34 novel microsatellite markers, genomic structure, and exclusion of six known genes in the region. 1095 Sep 23

Trefoil factor family (TFF) peptides promote cell migration, heal the mucosa and may suppress tumor growth. In reporter gene assays we show that aspirin (1-12 mM) evokes a six-fold up-regulation of TFF2, but not TFF1 and TFF3 transcription in human gastrointestinal cell lines. 6 h after application up-regulation of endogenous TFF2 mRNA was observed. TFF2 transcription was enhanced by indomethacin and arachidonic acid but repressed by staurosporine, suggesting mediation via protein kinase C. We mapped an aspirin responding element -546 to -758 bp upstream of TFF2. Up-regulation of TFF2 by aspirin may partially explain the chemopreventive potential of low dose aspirin in gastrointestinal carcinogenesis.
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PMID:Aspirin promotes TFF2 gene activation in human gastric cancer cell lines. 1116 73


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