Disease relevance of TFF2

• RESULTS: UACL glands containing TFF1 and TFF2 were observed in six patients with pouchitis [1].
• There was a significant correlation between TFF1 and TFF2 expression in gastric cancer and adjacent non-cancer tissues (p<0.001) [2].
• TFF2 expression was demonstrated in 87.5% of non-cancer patients, 34% of gastric carcinomas, and 58% of adjacent non-cancer tissues [2].
• In addition, a significantly higher prevalence of positive TFF2 staining was detected in large, diffuse tumors and in tumors with lymph node metastasis [3].
• RESULTS: Immunohistochemical tests for MUC2 and TFF2 were negative both in samples of Barret's metaplasia and in SCC [4].

Psychiatry related information on TFF2

• CONCLUSIONS: H. pylori infection, ageing, and sleep deprivation cause a reduction in the TFF2 diurnal rhythm [5].
• The neuropeptide substance P (SP) has been hypothesized to be involved in the etiopathology of affective disorders [6].
• This paper summarizes results of a series of experiments dealing with the effects of the neuropeptide substance P (SP) on avoidance learning and habituation [7].
• SP and DiMe-C7 reduced rearing and grooming behavior, whereas DiMe-C7 and SP(1-7) increased locomotor activity [8].
• Life stress and depression may be associated with altered blood levels of CNS-released neuropeptides, including substance P (SP) [9].

High impact information on TFF2

• Counterparts of skin tachykinins in mammalian tissues are SP, neurokinin A, and neurokinin B [10].
• Substance P (SP), first identified by bioassay as early as 1931 but sequenced only in 1971, several years after the elucidation of the structure of eledoisin from molluscan tissues and of physalaemin from amphibian skin, may be considered as a prototype of the tachykinins [10].
• Substance P (SP), a neurotachykinin, is important in a number of inflammatory processes in which the endothelial cell also plays a critical role [11].
• Autoradiographic ligand binding to human umbilical cord sections demonstrates the presence of SP binding sites with characteristics of the neurokinin 1 (NK-1) receptor (displacement by GTP analogues and the NK-1 specific antagonist CP-96,345) on human umbilical arterial, but not venous, endothelium [11].
• In culture, human umbilical venous endothelial cells (HUVECs) and human aortic endothelial cells express low levels of available SP binding sites [11].

Chemical compound and disease context of TFF2

• The human spasmolytic protein, SML1/hSP, an inhibitor of spasmolytic activity and gastric acid secretion in the pig, has been shown to exhibit homology to the pS2 protein, an estrogen-dependent breast cancer marker [12].
• Thus, TFF2 is an allergen-induced gene, which is expressed in mucus-positive airways, but is not a major contributor to allergen-induced goblet cell metaplasia, mucus production, or inflammatory responses in the lung [13].
• PBL chemotaxis to SP was abolished by inhibition of tyrosin kinase but not by that of protein kinase C. Preincubation of PBL with pertussis or cholera toxin inhibited SP chemotaxis, indicating that in PBL, NK receptors for chemotaxis probably are coupled with G protein and involve a tyrosin kinase signaling pathway [14].
• SP and NKA have links to the following chronic diseases: asthma, inflammatory bowel disorders, rheumatoid arthritis, pain and psychiatric disorders [15].
• We therefore used human astrocytoma cells to search for signal transduction cascades and transcription factors whose inhibition suppresses IL-6 synthesis after stimulation with three different inductors, IL-1beta, SP, and histamine [16].

Biological context of TFF2

• TFF1 and TFF2 proteins were localised by immunochemistry [1].
• CONCLUSION: These findings define USF factors as regulators of the TFF2 gene and suggest that promoter specific effects are important for a pronounced gene activation of this cytoprotective peptide [17].
• TFF2 did not induce phosphorylation of the epidermal growth factor (EGF) receptor [18].
• The motogenic activities of recombinant human TFF2 as well as porcine TFF2 were demonstrated by in vitro wound healing assays of BEAS-2B cells [18].
• There was no cross-reaction toward human TFF1 and TFF2 (40 nmol/L) [19].

Anatomical context of TFF2

• Aberrant expression of TFF1, TFF2, and TFF3 was frequently detected in gastric cell lines [2].
• BACKGROUND: The three trefoil factors (TFF1, TFF2, and TFF3) are small peptides believed to cross-link mucous glycoproteins and to play a role in the maintenance and repair of the gastrointestinal mucosa [19].
• Immunocytochemical staining of adult human pancreas showed abundant TFF3 immunoreactivity in pancreatic islets and some duct cells, whereas weak TFF1 and no TFF2 staining were detected [20].
• RESULTS: mRNA expression of TFF1 and TFF3, but not TFF2, was detected in human conjunctiva [21].
• RESULTS: mRNA expression of TFF1 and TFF3, but not TFF2, was detected in human lacrimal sac and nasolacrimal duct [22].

Associations of TFF2 with chemical compounds

• Indometacin-induced up-regulation of TFF2 expression was not antagonized by externally applied prostaglandin E2 [23].
• Since TFF peptides play an important role in gastric mucosal protection, indometacin-induced TFF2 may reduce the degree of gastric mucosal damage induced by indometacin [23].
• TFF1 and TFF2 mRNA levels were significantly up-regulated by the incubation of the cells with 15d-PGJ2 (10 micro m) or TGZ (30 micro m), whereas TFF3 mRNA level was not affected [24].
• 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 [25].
• There is a marked circadian variation in gastric luminal TFF2 in young healthy volunteers with peak levels present during the night [5].

Physical interactions of TFF2

• In contrast, pronounced binding differences were observed in cells with a strong preference for USF to interact specifically with the TFF2 E box, while Myc was not above background [17].
• Substance P (SP) participates in acute intestinal inflammation via binding to the G-protein-coupled neurokinin-1 receptor (NK-1R) and release of proinflammatory cytokines from colonic epithelial cells [26].

Enzymatic interactions of TFF2

• 5. Thus, there is neutral endopeptidase in the ferret trachea in vitro which cleaves exogenously applied SP and NKA, thereby reducing the magnitude and potency of their actions [27].

Regulatory relationships of TFF2

• TFF2 is co-expressed with TFF1 in gastric surface epithelial cells, but its potential role in vivo is unclear [25].
• TFF1 and TFF3 were mainly expressed in goblet cells and TFF2 in columnar cells in all the types of intestinal metaplasia [28].
• RESULTS: It was observed that the TFF2 promoter is specifically and efficiently activated by USF transcription factors but not by c-Myc [17].
• SP also stimulated IL-3-dependent colony formation of whole bone marrow MNCs in a soft agar culture system, but showed no such activity on isolated CD34+ cells in this system [29].
• Furthermore, SP can induce IL-1 type I receptor in stroma [30].

Other interactions of TFF2

• TFF3 mRNA localized patchily throughout the UACL, whereas TFF1 mRNA was found in the upper portions of the lineage and TFF2 mRNA and its product in the acini [31].
• TFF1, TFF2, and MUC6 were found in 84%, 92%, and 65% of GMD, respectively [32].
• MUC5AC and TFF2 were expressed at similar high levels in each clinical group [33].
• In small bile ducts, TFF2/DMBT1 is induced in damaged ducts irrespective of etiologies [34].
• Using specific inhibitors, the signaling cascades responsible for the motogenic response were shown to differ drastically when EGF was compared with TFF2 [35].

Analytical, diagnostic and therapeutic context of TFF2

• Only TFF2 was studied by immunohistochemistry, whereas the mRNAs for all three peptides were examined by in situ hybridization using 35S-labeled riboprobes [31].
• Neither TFF1 nor TFF2 expression was detected in ileal reservoirs without pouchitis [1].
• Data yielded by immunohistochemistry and RT-PCR showed a good correlation for both TFF1 and TFF2 [36].
• Both TFF3 and TFF2 were independent predictors of a worse disease-free survival [3].
• TFF2 did not affect cell motility in MCF-7 cells as measured by videomicroscopy, in contrast to previous studies using TFF1 [25].

References