Disease relevance of Tff3

• Mice lacking ITF had impaired mucosal healing and died from extensive colitis after oral administration of dextran sulfate sodium, an agent that causes mild epithelial injury in wild-type mice [1].
• CONCLUSIONS: These studies suggest that intestinal trefoil factor is involved in protection against and recovery from intestinal mucositis induced by radiation and chemotherapy [2].
• Mice given a complex inoculum of B. fragilis, enterococcus, and another anaerobe develop abscesses even after receiving column-purified ITF [3].
• ITF may function as an inhibitory factor for the growth of colonic neoplasm [4].
• To analyze the role of ITF in colon carcinomas, overexpression of the ITF gene in colon carcinoma cells was used [4].

High impact information on Tff3

• Impaired defense of intestinal mucosa in mice lacking intestinal trefoil factor [1].
• The gene encoding intestinal trefoil factor (ITF), a protein secreted throughout the small intestine and colon, was rendered nonfunctional in mice by targeted disruption [1].
• Despite the reduction in goblet-cell number, the total amount of ITF was increased in the mITF/DT-A transgenic mice, indicating inducible compensatory mechanisms [5].
• We administered 2 exogenous agents, dextran sodium sulfate (DSS) and acetic acid, to assess the susceptibility of mITF/DT-A transgenic mice to colonic injury [5].
• To assess the role of goblet cells in the intestine, we generated transgenic mice in which approximately 60% of goblet cells were ablated by the expression of an attenuated diphtheria toxin (DT) gene driven by the ITF promoter; other cell lineages were unaffected [5].

Chemical compound and disease context of Tff3

• The mITF expression was up-regulated during the recovery phase after depletion of goblet cells in acetic acid-induced colitis [6].
• Chronic administration of phenylbutazone, flufenamic acid and a new, potent non-steroidal anti-inflammatory agent ITF (3-methyl-5-benzoyl-amino-isothiazole-4-carboxy-p-ethoxyphenylamine) to BALB/c mice inoculated with a Moloney sarcoma virus resulted in a stimulation of tumor growth and increased severity of disease [7].

Biological context of Tff3

• METHODS: The effect of intestinal trefoil factor on migration and cell survival in intestinal epithelial monolayer exposed to methotrexate was studied in vitro [2].
• Further, inactivation of p21(WAF1/cip1) increased cell proliferation, decreased apoptosis, and decreased intestinal trefoil factor expression in the mucosa of both the small and large intestine [8].
• The mITF gene contains three exons distributed over 5 kb of genomic DNA [9].
• The gene encoding mouse intestinal trefoil factor: structural organization, partial sequence analysis and mapping to murine chromosome 17q [9].
• The genomic sequence is highly conserved, as compared with that of the rat and human ITF, and contains several AP-1-binding sites, the consensus binding site for the transcription factor Sp1, and a sequence homologous to a heat-shock element [9].

Anatomical context of Tff3

• Mice lacking ITF/TFF3 similarly made normal levels of goblet cell and Paneth cell responses [10].
• ITF/TFF3 appears not to influence cellular responses and does not alter parasite-induced pathological changes in the small intestine [10].
• SP and ITF levels in tissue fell within 48 h of ulceration (P < 0.05), but secretion into gastric juice was unchanged [11].
• Intestinal trefoil factor improved intestinal epithelial cell viability and wound repair after chemotherapy exposure in vitro [2].
• Effect of ectopic expression of rat trefoil factor family 3 (intestinal trefoil factor) in the jejunum of transgenic mice [12].

Associations of Tff3 with chemical compounds

• An ITF-expressing colonic (HT-ITF1) cell line was resistant to apoptosis induced by serum starvation and ceramide [13].
• The intraduodenal absorption of a new low-molecular-weight heparin (LMWH) diamine salt (ITF 1331) was compared with the parent compound ITF 1060 and with sodium LMWH, in anaesthetized rabbits [14].
• Data obtained with these new compounds showed that ITF 1697 has antianaphylactic activity, while ITF 2018 is endowed, mainly, with antiinflammatory activity [15].
• Two new chemical entities were studied according to this protocol: ITF 1697, a chemically stabilized C-reactive protein-derived tetrapeptide, and ITF 2018, a leflunomide analogue [15].
• Gene activation by EE was not required for inhibition of inflammatory gene expression, because both the phytoestrogen genistein and low doses of EE were effective in blocking inflammatory gene induction without inducing marker genes such as intestinal trefoil factor (ITF) or myo-inositol-1-phosphate synthase (IPS) [16].

Other interactions of Tff3

• Muc2 protein levels in the tissue were also maintained, however Tff3 protein levels were strongly decreased [17].
• ITF peptide expression was increased (as was SP expression) in wild-type but not knockout mice 42 and 72 days after injury (P < 0.05) [11].
• Northern blot analysis of various adult mouse tissues demonstrated that ITF is expressed abundantly in the intestine and colon, and minimally in stomach, but not in brain, lung, spleen, kidney, uterus, pancreas, liver, heart or thymus tissues [18].
• Northern blots were examined for somatostatin, intestinal trefoil factor and mucin-2 [19].

Analytical, diagnostic and therapeutic context of Tff3

• Studies were undertaken to define the role of intestinal trefoil factor in modulating the intestinal response to chemotherapy and radiation [2].
• Molecular cloning of mouse intestinal trefoil factor and its expression during goblet cell changes [6].
• Fluorescence in situ hybridization was used to assign ITF to chromosome 17 of the murine genome, a region syntenic with the trefoil gene cluster on human chromosome 21q22.3 [9].
• ITF not only colocalizes with MUC3, by confocal microscopy, to the apical surface of T84 cells following exposure to hypoxia, but is also found, by co-immunoprecipitation, to be physically associated with MUC3, following 24 h of hypoxia [20].
• The in vivo transcriptional interference was reciprocal, with EE induction of ITF and IPS greatly reduced in animals fed the atherogenic diet versus chow-fed controls [16].

References