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)

Human airway is generally destructed by inhaled factors and is the barrier to the external environment and has a crucial role in protection of the internal homeostasis of the lung. Sulfur mustard (SM) is a chemical warfare that capable of producing severe chemical injuries primarily in the lungs. Trefoil factor family (TFFs) plays major roles in epithelial repair and homeostasis, particularly in the lung. This study attempted to verify the role of TFFs in airway that induced by sulfur mustard. Fifteen patients exposed to SM and 10 non-exposed subjects were enrolled in this study. Bronchoscopy was carried out and endobronchial biopsy specimens were taken. The TFFs gene expressions were evaluated by RT-PCR. The results revealed that the TFF1 was overexpressed in exposed subjects in comparison to non-exposed subjects. In conclusion, TFF1 displays a distinct protein expression pattern in the developing of airway remodeling due to SM inhalation and plays an important role in maintaining the airway epithelium function.
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PMID:Trefoil Factor Family 1 Is Involved in Airway Remodeling of Mustard Lung. 2792 7

Trefoil factor (TFF) peptides, with a 40-amino acid motif and including six conserved cysteine residues that form intramolecular disulfide bonds, are a family of mucin-associated secretory molecules mediating many physiological roles that maintain and restore gastrointestinal (GI) mucosal homeostasis. TFF peptides play important roles in response to GI mucosal injury and inflammation. In response to acute GI mucosal injury, TFF peptides accelerate cell migration to seal the damaged area from luminal contents, whereas chronic inflammation leads to increased TFF expression to prevent further progression of disease. Although much evidence supports the physiological significance of TFF peptides in mucosal defenses, the molecular and cellular mechanisms of TFF peptides in the GI epithelium remain largely unknown. In this review, we summarize the functional roles of TFF1, 2, and 3 and illustrate their action mechanisms, focusing on defense mechanisms in the GI tract.
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PMID:Trefoil Factor Peptides and Gastrointestinal Function. 2799 33

Trefoil factor family (TFF) peptides have been shown to play a pivotal role in oncogenic transformation, tumorigenesis and metastasis by changing cell proliferation, apoptosis, migration and invasion behavior of various cancer cell lines. In the study presented, we investigated the effect of TFF1 overexpression on cell growth, viability, migration and tumorigenicity of different retinoblastoma (RB) cell lines. Transient TFF1 overexpression significantly increases RB cell apoptosis levels. Stable, lentiviral TFF1 overexpression likewise decreases RB cell viability, proliferation and growth and significantly increases apoptosis as revealed by WST-1 assays, BrdU and DAPI cell counts. TFF1-induced apoptosis is executed via cleaved caspase-3 activation as revealed by caspase blockage experiments and caspase-3 immunocytochemistry. Results from pG13-luciferase reporter assays and Western blot analyses indicate that TFF1-induced apoptosis is mediated through transcriptional activity of p53 with concurrently downregulated miR-18a expression. In ovo chicken chorioallantoic membrane (CAM) assays revealed that TFF1 overexpression significantly decreases the size of tumors forming from Y79 and RB355 cells and reduces the migration potential of RB355 cells. Differentially expressed genes and pathways involved in cancer progression were identified after TFF1 overexpression in Y79 cells by gene expression array analysis, underlining the effects on reduced tumorigenicity. TFF1 knockdown in RBL30 cells revealed caspase-3/7-independent apoptosis induction, but no changes on cell proliferation level. In summary, the in vitro and in vivo data demonstrate for the first time a tumor suppressor function of TFF1 in RB cells which is at least partly mediated by p53 activation and miR-18a downregulation.
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PMID:Reduction of the tumorigenic potential of human retinoblastoma cell lines by TFF1 overexpression involves p53/caspase signaling and miR-18a regulation. 2848 Oct 41

Gastroesophageal reflux disease (GERD) is a chronic disorder of the digestive tract characterised mainly by a heartburn. Being one of the most common gastrointestinal diseases, the prevalence of GERD reaches up to 25.9% in Europe. Barrett's esophagus (BE) is an acquired condition characterized by the replacement of the normal stratified squamous epithelium with metaplastic columnar epithelium. BE is believed to develop mainly from chronic GERD and is the most important risk factor of esophageal adenocarcinoma. Despite the availability of drugs such as proton pomp inhibitors and antacids, GERD is still a burden to local economy and impairs health-related quality of life in patients. Also, the endoscopic surveillance in patients with BE is burdensome and expensive what drives the need for biomarker of intestinal metaplasia and dysplasia. Trefoil factor family (TFF), consisting of TFF1, TFF2 and TFF3 peptides is gaining more and more attention due to its unique biochemical features and numerous functions. In this review the role of TFF1, TFF2 and TFF3 as potential treatment option and/or biomarker in the upper GI tract is discussed with particular focus on GERD and BE.
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PMID:Possible application of trefoil factor family peptides in gastroesophageal reflux and Barrett's esophagus. 3083 Nov 46

Trefoil factor family peptides (TFF1, TFF2, TFF3) are typically co-secreted together with mucins. Tff1 represents a gastric tumor suppressor gene in mice. TFFs are also synthesized in minute amounts in the immune and central nervous systems. In mucous epithelia, they support rapid repair by enhancing cell migration ("restitution") via their weak chemotactic and anti-apoptotic effects. For a long time, as a paradigm, this was considered as their major biological function. Within recent years, the formation of disulfide-linked heterodimers was documented for TFF1 and TFF3, e.g., with gastrokine-2 and IgG Fc binding protein (FCGBP). Furthermore, lectin activities were recognized as enabling binding to a lipopolysaccharide of Helicobacter pylori (TFF1, TFF3) or to a carbohydrate moiety of the mucin MUC6 (TFF2). Only recently, gastric TFF1 was demonstrated to occur predominantly in monomeric forms with an unusual free thiol group. Thus, a new picture emerged, pointing to diverse molecular functions for TFFs. Monomeric TFF1 might protect the gastric mucosa as a scavenger for extracellular reactive oxygen/nitrogen species. Whereas, the TFF2/MUC6 complex stabilizes the inner layer of the gastric mucus. In contrast, the TFF3-FCGBP heterodimer (and also TFF1-FCGBP) are likely part of the innate immune defense of mucous epithelia, preventing the infiltration of microorganisms.
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PMID:Trefoil Factor Family (TFF) Peptides and Their Diverse Molecular Functions in Mucus Barrier Protection and More: Changing the Paradigm. 3263 May 99

Trefoil factor family peptides (TFF1, TFF2, and TFF3) are key players in protecting, maintaining, and repairing the gastrointestinal tract. Accordingly, they have the therapeutic potential to treat and prevent a variety of gastrointestinal disorders associated with mucosal damage. TFF peptides share a conserved motif, including three disulfide bonds that stabilize a well-defined three-loop-structure reminiscent of a trefoil. Although multiple functions have been described for TFF peptides, their mechanisms at the molecular level remain poorly understood. This review presents the status quo of TFF research relating to gastrointestinal disorders. Putative TFF receptors and protein partners are described and critically evaluated. The therapeutic potential of these peptides in gastrointestinal disorders where altered mucosal biology plays a crucial role in the underlying etiology is discussed. Finally, areas of investigation that require further research are addressed. Thus, this review provides a comprehensive update on TFF literature as well as guidance toward future research to better understand this peptide family and its therapeutic potential for the treatment of gastrointestinal disorders.
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PMID:Structure, Function, and Therapeutic Potential of the Trefoil Factor Family in the Gastrointestinal Tract. 3283 64


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