This service exclusively searches for literature that cites resources. Please be aware that the total number of searchable documents is limited to those containing RRIDs and does not include all open-access literature.
Trefoil factors are essential healing initiators participating in mucosal reconstitution and tissue morphogenesis, especially on the surfaces of the gastrointestinal tract. This family has been cloned and characterized predominantly from mammals and amphibians. Avian species ingest stone and grit to help digest food, which may expose their gut to severe physical conditions. To further the understanding of the function of the TFF gene family across species, we undertook this research to clone, sequence, and characterize the spatio-temporal expression patterns of chicken TFF2 (ChTFF2) cDNA. Bioinformatics analysis of the promoter region and deduced amino acid sequence demonstrated that ChTFF2 contained unique characteristics; specifically the chicken promoter has multiple start sites and the protein contains a series of Lys-Lys-Val repeats. Unlike mammals, where TFF2 is detected primarily in the stomach, and occasionally in the proximal duodenum, chicken TFF2 transcripts are found throughout the gastrointestinal tract, with major expression sites in the glandular and muscular stomach as well as evident expression in the colon, small intestine, cecal tonsil and crop. Temporal analysis of intestinal ChTFF2 transcripts by quantitative RT-PCR showed high levels in embryos and a trend of constant expression during embryonic and post-hatch development, with a reduction occurring around hatch. Phylogenetic analysis highlighted the conservation of TFF proteins and functional divergence of trefoil domains, which suggest a transitional role in the bird during evolution.
Liver fibrosis is a common characteristic of chronic liver diseases. The activation of hepatic stellate cells (HSCs) plays a key role in fibrogenesis in response to liver injury, yet the mechanism by which damaged hepatocytes modulate the activation of HSCs is poorly understood. Our previous studies have established that liver-specific deletion of O-GlcNAc transferase (OGT)leads to hepatocyte necroptosis and spontaneous fibrosis. Here, we report that OGT-deficient hepatocytes secrete trefoil factor 2 (TFF2) that activates HSCs and contributes to the fibrogenic process. The expression and secretion of TFF2 are induced in OGT-deficient hepatocytes but not in WT hepatocytes. TFF2 activates the platelet-derived growth factor receptor beta signaling pathway that promotes the proliferation and migration of primary HSCs. TFF2 protein expression is elevated in mice with carbon tetrachloride-induced liver injury. These findings identify TFF2 as a novel factor that mediates intercellular signaling between hepatocytes and HSCs and suggest a role of the hepatic OGT-TFF2 axis in the process of fibrogenesis.
Trefoil factors (TFFs) are small secreted proteins that regulate tissue integrity and repair at mucosal surfaces, particularly in the gastrointestinal tract. However, their relative contribution(s) to controlling baseline lung function or the extent of infection-induced lung injury are unknown issues. With the use of irradiation bone marrow chimeras, we found that TFF2 produced from both hematopoietic- and nonhematopoietic-derived cells is essential for host protection, proliferation of alveolar type 2 cells, and restoration of pulmonary gas exchange after infection with the hookworm parasite Nippostrongylus brasiliensis. In the absence of TFF2, lung epithelia were unable to proliferate and expressed reduced lung mRNA transcript levels for type 2 response-inducing IL-25 and IL-33 after infectious injury. Strikingly, even in the absence of infection or irradiation, TFF2 deficiency compromised lung structure and function, as characterized by distended alveoli and reduced blood oxygen levels relative to wild-type control mice. Taken together, we show a previously unappreciated role for TFF2, produced by either hematopoietic or nonhematopoietic sources, as a pro-proliferative factor for lung epithelial cells under steady-state and infectious injury conditions.
The molecular mechanisms that drive mucosal T helper type 2 (T(H)2) responses against parasitic helminths and allergens remain unclear. In this study, we demonstrate in mice that TFF2 (trefoil factor 2), an epithelial cell-derived repair molecule, is needed for the control of lung injury caused by the hookworm parasite Nippostrongylus brasiliensis and for type 2 immunity after infection. TFF2 is also necessary for the rapid production of IL-33, a T(H)2-promoting cytokine, by lung epithelia, alveolar macrophages, and inflammatory dendritic cells in infected mice. TFF2 also increases the severity of allergic lung disease caused by house dust mite antigens or IL-13. Moreover, TFF2 messenger RNA expression is significantly increased in nasal mucosal brushings during asthma exacerbations in children. These experiments extend the biological functions of TFF2 from tissue repair to the initiation and maintenance of mucosal T(H)2 responses.
Determining the signalling cascade of epithelial repair, using murine gastric organoids, allows definition of regulatory processes intrinsic to epithelial cells, at the same time as validating and dissecting the signalling cascade with more precision than is possible in vivo Following single cell damage, intracellular calcium selectively increases within cells adjacent to the damage site and is essential for promoting repair. Trefoil factor 2 (TFF2) acts via chemokine C-X-C receptor 4 and epidermal growth factor receptor signalling, including extracellular signal-regulated kinase activation, to drive calcium mobilization and promote gastric repair. Sodium hydrogen exchanger 2, although essential for repair, acts downstream of TFF2 and calcium mobilization.
Protease-activated receptor 4 (PAR4), a member of G-protein coupled receptors family, was recently reported to exhibit decreased expression in gastric cancer and esophageal squamous cancer, yet increased expression during the progression of prostate cancer. Trefoil factor 2 (TFF2), a small peptide constitutively expressed in the gastric mucosa, plays a protective role in restitution of gastric mucosa. Altered TFF2 expression was also related to the development of gastrointestinal cancer. TFF2 has been verified to promote cell migration via PAR4, but the roles of PAR4 and TFF2 in the progress of colorectal cancer are still unknown. In this study, the expression level of PAR4 and TFF2 in colorectal cancer tissues was measured using real-time PCR (n = 38), western blotting (n=38) and tissue microarrays (n = 66). The mRNA and protein expression levels of PAR4 and TFF2 were remarkably increased in colorectal cancer compared with matched noncancerous tissues, especially in positive lymph node and poorly differentiated cancers. The colorectal carcinoma cell LoVo showed an increased response to TFF2 as assessed by cell invasion upon PAR4 expression. However, after intervention of PAR4 expression, PAR4 positive colorectal carcinoma cell HT-29 was less responsive to TFF2 in cell invasion. Genomic bisulfite sequencing showed the hypomethylation of PAR4 promoter in colorectal cancer tissues and the hypermethylation in the normal mucosa that suggested the low methylation of promoter was correlated to the increased PAR4 expression. Taken together, the results demonstrated that the up-regulated expression of PAR4 and TFF2 frequently occurs in colorectal cancer tissues, and that overexpression of PAR4 may be resulted from promoter hypomethylation. While TFF2 promotes invasion activity of LoVo cells overexpressing PAR4, and this effect was significantly decreased when PAR4 was knockdowned in HT-29 cells. Our findings will be helpful in further investigations into the functions and molecular mechanisms of Proteinase-activated receptors (PARs) and Trefoil factor factors (TFFs) during the progression of colorectal cancer.
Coordinated efforts between macrophages and epithelia are considered essential for wound healing, but the macrophage-derived molecules responsible for repair are poorly defined. This work demonstrates that lung macrophages rely upon Trefoil factor 2 to promote epithelial proliferation following damage caused by sterile wounding, Nippostrongylus brasiliensis or Bleomycin sulfate. Unexpectedly, the presence of T, B, or ILC populations was not essential for macrophage-driven repair. Instead, conditional deletion of TFF2 in myeloid-restricted CD11cCre TFF2 flox mice exacerbated lung pathology and reduced the proliferative expansion of CD45- EpCAM+ pro-SPC+ alveolar type 2 cells. TFF2 deficient macrophages had reduced expression of the Wnt genes Wnt4 and Wnt16 and reconstitution of hookworm-infected CD11cCre TFF2flox mice with rWnt4 and rWnt16 restored the proliferative defect in lung epithelia post-injury. These data reveal a previously unrecognized mechanism wherein lung myeloid phagocytes utilize a TFF2/Wnt axis as a mechanism that drives epithelial proliferation following lung injury.
Pancreatic cancer is a challenging disease with a high mortality rate. While the importance of crosstalk between cancer and immune cells has been well documented, the understanding of this complex molecular network is incomplete. Thus, identification of the secreted proteins contributing to the immunosuppressive microenvironment in pancreatic cancer is crucial for effective diagnosis and/or therapy. We utilized a public microarray dataset (GSE16515) from the Gene Expression Omnibus database to identify genes for secreted proteins in pancreatic cancer. RT-PCR and ELISA of the pancreatic cancer cell lines validated the cellular origin of the selected genes. For functional assay of the selected proteins, we utilized human-monocyte-derived dendritic cells (DCs). From the list of the secreted proteins, trefoil factor 2 (TFF2) was further examined as a potential chemokine/cytokine. While TFF2 did not significantly affect the phenotypic maturation and the allostimulatory capacity of DCs, TFF2 preferentially attracted immature (but not mature) DCs and inhibited their endocytic activity. Our data suggest that TFF2 from pancreatic cancer cells may attract immature DCs and affect the initial stage of DC maturation, thereby contributing to the induction of immune tolerance against pancreatic cancer.
The preservation of pancreatic β-cell mass is an essential factor in the onset and development of type 2 diabetes mellitus. Recently, sodium-glucose cotransporter 2 inhibitors have been launched as antihyperglycemic agents, and their organ-protective effects are attracting attention. They are also reported to have favorable effects on the preservation of pancreatic β-cell mass, but the appropriate timing for the administration of sodium-glucose cotransporter 2 inhibitors is obscure.
Although IL-6-mediated activation of the signal transduction and activator of transcription 3 (STAT3) axis is involved in inflammation and cancer, the role of STAT3 in Helicobacter-associated gastric inflammation and carcinogenesis is unclear. This study investigated the role of STAT3 in gastric inflammation and carcinogenesis and examined the molecular mechanism of Helicobacter-induced gastric phenotypes.
Proton pump inhibitor use is associated with an increased risk of gastric cancer, which may be mediated by hypergastrinemia. Spasmolytic polypeptide-expression metaplasia (SPEM) has been proposed as a precursor of gastric cancer. We have examined the effects of the gastrin receptor antagonist netazepide (NTZ) or vehicle on the gastric corpus mucosa of H+/K+ATPase beta subunit knockout (KO) and wild-type (WT) mice. The gastric corpus was evaluated by histopathology, immunohistochemistry (IHC), in situ hybridization (ISH) and whole-genome gene expression analysis, focusing on markers of SPEM and neuroendocrine (NE) cells. KO mice had pronounced hypertrophy, intra- and submucosal cysts and extensive expression of SPEM and NE cell markers in the gastric corpus, but not in the antrum. Numerous SPEM-related genes were upregulated in KO mice compared to WT mice. NTZ reduced hypertrophia, cysts, inflammation and NE hyperplasia. However, NTZ neither affected expression of SPEM markers nor of SPEM-related genes. In conclusion, NTZ prevented mucosal hypertrophy, cyst formation and NE cell hyperplasia but did not affect SPEM. The presence of SPEM seems unrelated to the changes caused by hypergastrinemia in this animal model.
Trefoil factors, which bear a unique 3-loop trefoil domain, are a family of small secretory protease-resistant peptides (7-12 kDa) discovered in the 1980s. Trefoil factor 2 (TFF2) is a unique member of trefoil factors family that plays important roles in gastrointestinal mucosal defense and repair. However, few studies have characterized the miRNA expression patterns in TFF2 knock-out mice. In this study, we investigated the regulatory role of miRNAs in TFF2 knock-out mice. Whole miRNome profiling for TFF2 knock-out mice and wild-type mice were downloaded from the Gene Expression Omnibus database. A total of 14 differentially expressed miRNAs were identified using the limma package. Target genes for 2 differentially expressed miRNAs were retrieved from 2 databases. After mapping these target genes into STRING, an interaction network was constructed. Gene Ontology analysis suggested that the differentially expressed miRNAs are involved in cyclic AMP metabolism and the growth process. Additionally, dysregulated miRNAs target pathways of transforming growth factor-beta signaling pathway and cytokine-cytokine receptor interaction. Our results suggest that miRNAs may play important regulatory roles in processes involving TFF2, particularly in the regulation of signal transduction pathways. However, further validation of our results is needed.
During aging, physiological changes in the stomach result in more tenuous gastric tissue that is less capable of repairing injury, leading to increased susceptibility to chronic ulceration. Spasmolytic polypeptide/trefoil factor 2-expressing metaplasia (SPEM) is known to emerge after parietal cell loss and during Helicobacter pylori infection, however, its role in gastric ulcer repair is unknown. Therefore, we sought to investigate if SPEM plays a role in epithelial regeneration.
Trefoil factor 2 (TFF2) is a member of trefoil factor family found to be overexpressed in many cancers including cholangiocarcinoma (CCA). The majority of studies have focused on wild-type TFF2 (wtTFF2) expression, but information regarding alternative splicing variants of TFF2 mRNA has not been reported. In this study, we aimed to identify and quantify a novel TFF2 splice variant in cholangiocarcinoma (CCA). Seventy-eight tumors and 15 normal adjacent tissues were quantified for the expression of the TFF2 splice variant relative to wild-type (wt) TFF2 mRNA using quantitative reverse transcriptase polymerase chain reaction (QRT-PCR). The ratio of TFF2 splice variant against wtTFF2 was analyzed for associations with clinical parameters. We found a novel TFF2 splice variant, exon 2 skipping (∆EX2TFF2), resulting in a stop codon (TAG) at exon 1. The ∆EX2TFF2/wtTFF2 ratio in tumors was significantly higher than in normal tissue (P<0.01). Interestingly, high ∆EX2TFF2/wtTFF2 ratio was significantly associated with good prognosis compared with low ratio (P=0.017). In contrast, the presence of wtTFF2 protein was associated with poor survival of CCA patients (P=0.034). This is the first report of a trefoil factor splice variant and its potential application as a prognostic biomarker in CCA.
Biomarkers for early diagnosis of pancreatic cancer are greatly needed, as the high fatality of this cancer is in part due to delayed detection. α1,4-linked N-acetylglucosamine (αGlcNAc), a unique O-glycan specific to gastric gland mucus, is biosynthesized by α1,4-N-acetylglucosaminyltransferase (α4GnT) and primarily bound at the terminal glycosylated residue to scaffold protein MUC6. We previously reported that αGlcNAc expression decreases at early stages of neoplastic pancreatic lesions, followed by decreased MUC6 expression, although functional effects of these outcomes were unknown. Here, we ectopically expressed α4GnT, the αGlcNAc biosynthetic enzyme, together with MUC6 in the human pancreatic cancer cell lines MIA PaCa-2 and PANC-1, neither of which expresses α4GnT and MUC6. We observed significantly suppressed proliferation in both lines following coexpression of α4GnT and MUC6. Moreover, cellular motility decreased following MUC6 ectopic expression, an effect enhanced by cotransduction with α4GnT. MUC6 expression also attenuated invasiveness of both lines relative to controls, and this effect was also enhanced by additional α4GnT expression. We found αGlcNAc-bound MUC6 formed a complex with trefoil factor 2. Furthermore, analysis of survival curves of patients with pancreatic ductal adenocarcinoma using a gene expression database showed that samples marked by higher A4GNT or MUC6 mRNA levels were associated with relatively favorable prognosis. These results strongly suggest that αGlcNAc and MUC6 function as tumor suppressors in pancreatic cancer and that decreased expression of both may serve as a biomarker of tumor progression to pancreatic cancer.
This study was designed to determine whether α-humulene, a major constituent in many plants used in fragrances, has a protective role against gastric injury in vivo and in vitro. A rat model of hydrochloric acid (HCl)/ethanol-induced gastritis and human mast cells (HMC-1) were used to investigate the mucosal protective effect of α-humulene. α-Humulene significantly inhibited gastric lesions in HCl/ethanol-induced acute gastritis and decreased gastric acid secretion pyloric ligation-induced gastric ulcers in vivo. In addition, α-humulene reduced the amount of reactive oxygen species and malondialdehyde through upregulation of prostaglandin E2 (PGE2) and superoxide dismutase (SOD). In HMC-1 cells, α-humulene decreased intracellular calcium and increased intracellular cyclic adenosine monophosphate (cAMP) levels, resulting in low histamine levels. α-Humulene also reduced the expression levels of cytokine genes such as interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF) by downregulating nuclear factor-κB (NF-κB) nuclear translocation. Finally, α-humulene upregulated the expression levels of mucin 5AC (Muc5ac), Muc6, trefoil factor 1 (Tff1), trefoil factor 2 (Tff2), and polymeric immunoglobulin receptor (pigr). α-Humulene may attenuate HCl/ethanol-induced gastritis by inhibiting histamine release and NF-κB activation and stimulating antioxidants and mucosal protective factors, particularly Muc5ac and Muc6. Therefore, these data suggest that α-humulene is a potential drug candidate for the treatment of stress-induced or alcoholic gastritis.
Two experiments were performed to investigate the effect of different ratios of arginine (Arg) to lysine (Lys) in diets with low (30% Lys; Experiment 1) and high (45% Lys; Experiment 2) methionine (Met) levels on selected metabolic parameters, oxidative and epigenetic DNA damage, and the mechanisms underlying intestinal barrier integrity in turkeys challenged with Clostridium perfringens. In each experiment, 108 one-day-old Hybrid Converter female turkeys were placed in 6 pens (18 birds per pen) and reared for 42 days. At 34, 36 and 37 days of age, half of the birds were subjected to C. perfringens challenge. A 3 × 2 factorial design with three levels of Arg relative to Lys (90, 100 and 110%; Arg90, Arg100 and Arg110, respectively) and C. perfringens infection (-, +) was employed. Challenging birds with C. perfringens increased lipid oxidation and the oxidation and methylation of DNA of intestinal mucosa, and down-regulated the activities of DNA-repairing enzymes. Neither the dietary treatment nor the challenge affected the markers of liver function or metabolism. Arg110 diets with the high Met level induced DNA oxidation and methylation whereas these processes were downregulated in birds fed Arg90 diets. The results indicate that Arg90 diets with high Met levels have a beneficial influence on the indicators of intestinal barrier integrity in turkeys with necrotic enteritis (NE). Despite the analyzed amino acid ratios interacted with the systems responsible for the maintenance of gut integrity in the host organism, this dietary intervention probably enabled birds to cope with NE.
A subset of myeloid-derived suppressor cells (MDSCs) that express murine Schlafen4 (SLFN4) or its human ortholog SLFN12L polarize in the Helicobacter-inflamed stomach coincident with intestinal or spasmolytic polypeptide-expressing metaplasia. We propose that individuals with a more robust response to damage-activated molecular patterns and increased Toll-like receptor 9 (TLR9) expression are predisposed to the neoplastic complications of Helicobacter infection.
The molecular transducers conferring the benefits of chronic exercise in diabetes prevention remain to be comprehensively investigated. Herein, serum proteomic profiling of 688 inflammatory and metabolic biomarkers in 36 medication-naive overweight and obese men with prediabetes reveals hundreds of exercise-responsive proteins modulated by 12-week high-intensity interval exercise training, including regulators of metabolism, cardiovascular system, inflammation, and apoptosis. Strong associations are found between proteins involved in gastro-intestinal mucosal immunity and metabolic outcomes. Exercise-induced changes in trefoil factor 2 (TFF2) are associated with changes in insulin resistance and fasting insulin, whereas baseline levels of the pancreatic secretory granule membrane major glycoprotein GP2 are related to changes in fasting glucose and glucose tolerance. A hybrid set of 23 proteins including TFF2 are differentially altered in exercise responders and non-responders. Furthermore, a machine-learning algorithm integrating baseline proteomic signatures accurately predicts individualized metabolic responsiveness to exercise training.
Welcome to the FDI Lab - SciCrunch.org Resources search. From here you can search through a compilation of resources used by FDI Lab - SciCrunch.org and see how data is organized within our community.
You are currently on the Community Resources tab looking through categories and sources that FDI Lab - SciCrunch.org has compiled. You can navigate through those categories from here or change to a different tab to execute your search through. Each tab gives a different perspective on data.
If you have an account on FDI Lab - SciCrunch.org then you can log in from here to get additional features in FDI Lab - SciCrunch.org such as Collections, Saved Searches, and managing Resources.
Here is the search term that is being executed, you can type in anything you want to search for. Some tips to help searching:
You can save any searches you perform for quick access to later from here.
We recognized your search term and included synonyms and inferred terms along side your term to help get the data you are looking for.
If you are logged into FDI Lab - SciCrunch.org you can add data records to your collections to create custom spreadsheets across multiple sources of data.
Here are the facets that you can filter your papers by.
From here we'll present any options for the literature, such as exporting your current results.
If you have any further questions please check out our FAQs Page to ask questions and see our tutorials. Click this button to view this tutorial again.
Year:
Count: