Gene Symbol: Tff3
Description: trefoil factor 3, intestinal
Alias: ITF, mITF, trefoil factor 3, intestinal trefoil factor
Species: mouse
Products:     Tff3

Top Publications

  1. Okubo T, Hogan B. Hyperactive Wnt signaling changes the developmental potential of embryonic lung endoderm. J Biol. 2004;3:11 pubmed
    ..We discuss the relevance of our findings to the poorly understood pathological condition of intestinal metaplasia in humans. ..
  2. Lubka M, Müller M, Baus Loncar M, Hinz M, Blaschke K, Hoffmann W, et al. Lack of Tff3 peptide results in hearing impairment and accelerated presbyacusis. Cell Physiol Biochem. 2008;21:437-44 pubmed publisher
    ..Here we present new data about Tff3 expression in the cochlea of the rodent inner ear...
  3. Jiang H, Przybyszewski J, Mitra D, Becker C, Brehm Stecher B, Tentinger A, et al. Soy protein diet, but not Lactobacillus rhamnosus GG, decreases mucin-1, trefoil factor-3, and tumor necrosis factor-? in colon of dextran sodium sulfate-treated C57BL/6 mice. J Nutr. 2011;141:1239-46 pubmed publisher
    ..There was no overall effect of LGG on these measurements. In conclusion, soy protein suppressed the DSS-induced inflammatory stimulation of MUC, TFF, and TNF? gene expression independently of LGG. ..
  4. Chinery R, Poulsom R, Cox H. The gene encoding mouse intestinal trefoil factor: structural organization, partial sequence analysis and mapping to murine chromosome 17q. Gene. 1996;171:249-53 pubmed
    ..In the present study, the nucleotide sequence of a large portion (81%) of the gene encoding murine intestinal trefoil factor (mITF) and its whole genomic organization were determined...
  5. Mashimo H, Wu D, Podolsky D, Fishman M. Impaired defense of intestinal mucosa in mice lacking intestinal trefoil factor. Science. 1996;274:262-5 pubmed
    ..The gene encoding intestinal trefoil factor (ITF), a protein secreted throughout the small intestine and colon, was rendered nonfunctional in mice ..
  6. Burmeister M, Meyer G. The trefoil gene maps to mouse chromosome 17. Mamm Genome. 1997;8:223-4 pubmed
  7. Zhu Y, Zhao S, Deng Y, Gordillo R, Ghaben A, Shao M, et al. Hepatic GALE Regulates Whole-Body Glucose Homeostasis by Modulating Tff3 Expression. Diabetes. 2017;66:2789-2799 pubmed publisher
    ..Transcriptional profiling identifies trefoil factor 3 (Tff3) as one of the downstream targets of GALE...
  8. Reynolds S, Zemke A, Giangreco A, Brockway B, Teisanu R, Drake J, et al. Conditional stabilization of beta-catenin expands the pool of lung stem cells. Stem Cells. 2008;26:1337-46 pubmed publisher
    ..Our data demonstrate that the differentiation-modulating activities of stabilized beta-catenin account for expansion of tissue stem cells. ..
  9. Bijelić N, Belovari T, Baus Loncar M. Trefoil factor family protein 3 (TFF3) is present in cartilage during endochondral ossification in the developing mouse fetus. Acta Histochem. 2013;115:204-8 pubmed publisher
    Trefoil factor family protein 3 (TFF3) is found in cartilage affected by osteoarthritis and septic arthritis, whereas no TFF3 presence is observed in healthy cartilage...

More Information


  1. Kont V, Laan M, Kisand K, Merits A, Scott H, Peterson P. Modulation of Aire regulates the expression of tissue-restricted antigens. Mol Immunol. 2008;45:25-33 pubmed
    ..The data underline a direct role for Aire in TRA expression and suggest that modulation of Aire has a potential to control central tolerance and autoimmunity. ..
  2. Babeu J, Darsigny M, Lussier C, Boudreau F. Hepatocyte nuclear factor 4alpha contributes to an intestinal epithelial phenotype in vitro and plays a partial role in mouse intestinal epithelium differentiation. Am J Physiol Gastrointest Liver Physiol. 2009;297:G124-34 pubmed publisher
  3. Belovari T, Bijelić N, Tolušić Levak M, Baus Lončar M. Trefoil factor family peptides TFF1 and TFF3 in the nervous tissues of developing mouse embryo. Bosn J Basic Med Sci. 2015;15:33-7 pubmed publisher
    Trefoil factor family peptides (TFF1, TFF2, and TFF3) are predominantly found in mucous epithelia of various organs. However, they have also been reported in the nervous tissue, particularly mouse, rat, porcine, and human brain...
  4. Podolsky D, Gerken G, Eyking A, Cario E. Colitis-associated variant of TLR2 causes impaired mucosal repair because of TFF3 deficiency. Gastroenterology. 2009;137:209-20 pubmed publisher
    ..Dextran sulfate sodium (DSS) colitis was induced in wild-type, TFF3(-/-), and TLR2(-/-) mice. Recombinant TLR2 ligand or TFF3 peptide were orally administered after DSS termination...
  5. Kim B, Miletich I, Mao J, McMahon A, Sharpe P, Shivdasani R. Independent functions and mechanisms for homeobox gene Barx1 in patterning mouse stomach and spleen. Development. 2007;134:3603-13 pubmed
    ..These observations place Barx1 proximally within a Wt1 pathway of spleen development and reveal how a homeotic regulator employs different molecular mechanisms to mold neighboring organs. ..
  6. Marchbank T, Cox H, Goodlad R, Giraud A, Moss S, Poulsom R, et al. Effect of ectopic expression of rat trefoil factor family 3 (intestinal trefoil factor) in the jejunum of transgenic mice. J Biol Chem. 2001;276:24088-96 pubmed
    ..of which is up-regulated at sites of injury, we have produced transgenic mice that chronically express rat TFF3 within the jejunum (using a rat fatty acid-binding protein promoter)...
  7. Zhang Y, Goss A, Cohen E, Kadzik R, Lepore J, Muthukumaraswamy K, et al. A Gata6-Wnt pathway required for epithelial stem cell development and airway regeneration. Nat Genet. 2008;40:862-70 pubmed publisher
    ..Together, these data demonstrate that Gata6-regulated Wnt signaling controls the balance between progenitor expansion and epithelial differentiation required for both lung development and regeneration. ..
  8. Okada H, Kimura M, Tan D, Fujiwara K, Igarashi J, Makuuchi M, et al. Frequent trefoil factor 3 (TFF3) overexpression and promoter hypomethylation in mouse and human hepatocellular carcinomas. Int J Oncol. 2005;26:369-77 pubmed
    Expression profiling analysis revealed ectopic high expression of mouse TFF3 in non-tumor liver tissues from the hepatocellular carcinoma (HCC) susceptible PWK/Rbrc strain...
  9. Thiem S, Eissmann M, Stuart E, Elzer J, Jonas A, Buchert M, et al. Inducible gene modification in the gastric epithelium of Tff1-CreERT2, Tff2-rtTA, Tff3-luc mice. Genesis. 2016;54:626-635 pubmed publisher
    ..The Tg(Tff1-CreERT2;Tff2-rtTA;Tff3-Luc) strain confers tamoxifen-inducible irreversible somatic recombination and allows simultaneous doxycycline-..
  10. Tebbutt N, Giraud A, Inglese M, Jenkins B, Waring P, Clay F, et al. Reciprocal regulation of gastrointestinal homeostasis by SHP2 and STAT-mediated trefoil gene activation in gp130 mutant mice. Nat Med. 2002;8:1089-97 pubmed
    ..are highly similar to the phenotypes exhibited by mice deficient in trefoil factor 1 (pS2/TFF1) and intestinal trefoil factor (ITF)/TFF3, respectively, and corresponded closely with the capacity of the two pathways to stimulate ..
  11. Gregorieff A, Stange D, Kujala P, Begthel H, van den Born M, Korving J, et al. The ets-domain transcription factor Spdef promotes maturation of goblet and paneth cells in the intestinal epithelium. Gastroenterology. 2009;137:1333-45.e1-3 pubmed publisher
    ..In this study, we investigated the role of the Wnt-responsive, Ets-domain transcription factor Spdef in the differentiation of goblet and Paneth cells...
  12. Lubka Pathak M, Shah A, Gallozzi M, Muller M, Zimmermann U, Löwenheim H, et al. Altered expression of securin (Pttg1) and serpina3n in the auditory system of hearing-impaired Tff3-deficient mice. Cell Mol Life Sci. 2011;68:2739-49 pubmed publisher
    b>Tff3 peptide exerts important functions in cytoprotection and restitution of the gastrointestinal (GI) tract epithelia. Moreover, its presence in the rodent inner ear and involvement in the hearing process was demonstrated recently...
  13. Beck P, Wong J, Li Y, Swaminathan S, Xavier R, Devaney K, et al. Chemotherapy- and radiotherapy-induced intestinal damage is regulated by intestinal trefoil factor. Gastroenterology. 2004;126:796-808 pubmed
    ..Studies were undertaken to define the role of intestinal trefoil factor in modulating the intestinal response to chemotherapy and radiation...
  14. Shen J, Liu J, Xie Y, Diwan B, Waalkes M. Fetal onset of aberrant gene expression relevant to pulmonary carcinogenesis in lung adenocarcinoma development induced by in utero arsenic exposure. Toxicol Sci. 2007;95:313-20 pubmed
    ..These data provide evidence that arsenic-induced aberrant ER signaling could disrupt early life stage genetic programing in the lung leading eventually to lung tumor formation much later in adulthood. ..
  15. Paulsen F, Woon C, Varoga D, Jansen A, Garreis F, Jäger K, et al. Intestinal trefoil factor/TFF3 promotes re-epithelialization of corneal wounds. J Biol Chem. 2008;283:13418-27 pubmed publisher using cornea as a model, we demonstrate the importance of trefoil factor 3 (TFF3, also known as intestinal trefoil factor) in re-epithelialization of wounds...
  16. Mashimo H, Podolsky D, Fishman M. Structure and expression of murine intestinal trefoil factor: high evolutionary conservation and postnatal expression. Biochem Biophys Res Commun. 1995;210:31-7 pubmed
    b>Intestinal Trefoil Factor (ITF) is a member of a family of gastrointestinal tract peptides with region-specific expression which are enhanced at sites of injury and repair...
  17. Ge H, Gardner J, Wu X, Rulifson I, Wang J, Xiong Y, et al. Trefoil Factor 3 (TFF3) Is Regulated by Food Intake, Improves Glucose Tolerance and Induces Mucinous Metaplasia. PLoS ONE. 2015;10:e0126924 pubmed publisher
    Trefoil factor 3 (TFF3), also called intestinal trefoil factor or Itf, is a 59 amino acid peptide found as a homodimer predominantly along the gastrointestinal tract and in serum...
  18. Xue Y, Shen L, Cui Y, Zhang H, Chen Q, Cui A, et al. Tff3, as a novel peptide, regulates hepatic glucose metabolism. PLoS ONE. 2013;8:e75240 pubmed publisher
    ..The trefoil peptides are a family of small regulatory proteins and Tff3 is widely expressed in multiple tissues including liver...
  19. Samant S, Fossella J, Silver L, Pilder S. Mapping and cloning recombinant breakpoints demarcating the hybrid sterility 6-specific sperm tail assembly defect. Mamm Genome. 1999;10:88-94 pubmed
    ..In addition, we have provided increased high-resolution mapping of the Stop1p and Ccub factors. These new data enhance our ability to isolate and characterize candidates for Tcd/Tcs2. ..
  20. Nyeng P, Norgaard G, Kobberup S, Jensen J. FGF10 maintains distal lung bud epithelium and excessive signaling leads to progenitor state arrest, distalization, and goblet cell metaplasia. BMC Dev Biol. 2008;8:2 pubmed publisher
  21. Comelli E, Simmering R, Faure M, Donnicola D, Mansourian R, Rochat F, et al. Multifaceted transcriptional regulation of the murine intestinal mucus layer by endogenous microbiota. Genomics. 2008;91:70-7 pubmed
    ..We found that the expression of mucins 1 to 4 and trefoil factor 3 was down-regulated in the ileum and colon of conventional and reconventionalized mice compared with germ-free ..
  22. Lefebvre O, Chenard M, Masson R, Linares J, Dierich A, LeMeur M, et al. Gastric mucosa abnormalities and tumorigenesis in mice lacking the pS2 trefoil protein. Science. 1996;274:259-62 pubmed
    ..These results indicate that mpS2 is essential for normal differentiation of the antral and pyloric gastric mucosa and may function as a gastric-specific tumor suppressor gene. ..
  23. Itoh H, Inoue N, Podolsky D. Goblet-cell-specific transcription of mouse intestinal trefoil factor gene results from collaboration of complex series of positive and negative regulatory elements. Biochem J. 1999;341 ( Pt 2):461-72 pubmed
    b>Intestinal trefoil factor (ITF) is expressed selectively in intestinal goblet cells...
  24. Tomasetto C, Masson R, Linares J, Wendling C, Lefebvre O, Chenard M, et al. pS2/TFF1 interacts directly with the VWFC cysteine-rich domains of mucins. Gastroenterology. 2000;118:70-80 pubmed
  25. Tomita M, Itoh H, Ishikawa N, Higa A, Ide H, Murakumo Y, et al. Molecular cloning of mouse intestinal trefoil factor and its expression during goblet cell changes. Biochem J. 1995;311 ( Pt 1):293-7 pubmed
    A cDNA encoding mouse intestinal trefoil factor (mITF) was successfully cloned and sequenced from the small intestine of C57BL/6 mouse by using the combination of reverse transcription-PCR and rapid amplification of cDNA ends methods...
  26. Manko A, Motta J, Cotton J, Feener T, Oyeyemi A, Vallance B, et al. Giardia co-infection promotes the secretion of antimicrobial peptides beta-defensin 2 and trefoil factor 3 and attenuates attaching and effacing bacteria-induced intestinal disease. PLoS ONE. 2017;12:e0178647 pubmed publisher
    ..concurrently enhancing the production and secretion of antimicrobial peptides (AMPs) mouse ?-defensin 3 and trefoil factor 3 (TFF3). Co-infection of human intestinal epithelial cells (Caco-2) monolayers with G...
  27. Otto W, Patel K. Trefoil factor family (TFF)-domain peptides in the mouse: embryonic gastrointestinal expression and wounding response. Anat Embryol (Berl). 1999;199:499-508 pubmed
    ..Afterwards, TFF2 was confined to the gastric region. TFF3 was in the stomach at E13. On E15 and 16 TFF3 was ubiquitous, except for E15 caecum...
  28. Park Y, Franklin J, Settle S, Levy S, Chung E, Jeyakumar L, et al. Gene expression profile analysis of mouse colon embryonic development. Genesis. 2005;41:1-12 pubmed
  29. Shi H, Yin X, Song L, Guo Q, Luo X. Neuropeptide Trefoil factor 3 improves learning and retention of novel object recognition memory in mice. Behav Brain Res. 2012;227:265-9 pubmed publisher
    ..However, to date, no study has investigated the effects of neuropeptide Trefoil factor 3 (TFF3) on the process of learning and memory...
  30. Fossella J, Samant S, Silver L, King S, Vaughan K, Olds Clarke P, et al. An axonemal dynein at the Hybrid Sterility 6 locus: implications for t haplotype-specific male sterility and the evolution of species barriers. Mamm Genome. 2000;11:8-15 pubmed
    ..Our results argue that Dnahc8 is fundamental to flagellar organization and function in Domesticus, but not Spretus, and suggest that Dnahc8 is integral to both Hst6- and t-specific male infertility. ..
  31. Liu S, Roberts D, Zhang B, Ren Y, Zhang L, Wu Y. Trefoil factor 3 as an endocrine neuroprotective factor from the liver in experimental cerebral ischemia/reperfusion injury. PLoS ONE. 2013;8:e77732 pubmed publisher
    ..experimental cerebral ischemia/reperfusion injury in the mouse causes upregulation of the secretory protein trefoil factor 3 (TFF3) in the hepatocyte in association with an increase in serum TFF3...
  32. Beck P, Ihara E, Hirota S, MacDonald J, Meng D, Nanthakumar N, et al. Exploring the interplay of barrier function and leukocyte recruitment in intestinal inflammation by targeting fucosyltransferase VII and trefoil factor 3. Am J Physiol Gastrointest Liver Physiol. 2010;299:G43-53 pubmed publisher
    ..b>Trefoil factor 3 (TFF3) is involved in both protecting the intestinal epithelium against injury as well as aiding in wound ..
  33. Ribieras S, Lefebvre O, Tomasetto C, Rio M. Mouse Trefoil factor genes: genomic organization, sequences and methylation analyses. Gene. 2001;266:67-75 pubmed
    The mammalian Trefoil Factors (TFFs), TFF1/pS2, TFF2/SP and TFF3/ITF, are expressed and secreted throughout the gastrointestinal tract with a specific and complementary pattern...
  34. Grainger S, Lam J, Savory J, Mears A, Rijli F, Lohnes D. Cdx regulates Dll1 in multiple lineages. Dev Biol. 2012;361:1-11 pubmed publisher
    ..These findings suggest that Cdx members operate upstream of Dll1 to convey different functions in two distinct lineages. ..
  35. Shah A, Leidinger P, Keller A, Wendschlag A, Backes C, Baus Loncar M, et al. The intestinal factor Tff3 and a miRNA network regulate murine caloric metabolism. RNA Biol. 2011;8:77-81 pubmed
    ..The trefoil peptides also appear involved in caloric metabolism. Monitoring global miRNA expression of Tff3 deficient mice points to an interplay of Tff3 with a miRNA regulatory network...
  36. Jacquemin P, Chen Z, Martial J, Davidson I. Genomic structure and chromosomal mapping of the mouse transcription factor TEF-5 (Tead3) gene. Mamm Genome. 1999;10:632-4 pubmed
  37. Kawashima T, Okamoto K, Muraguchi T, Oku T, Shidoji Y. Downregulation of trefoil factor 3 gene expression in the colon of the senescence-accelerated mouse (SAM)-P6 revealed by oligonucleotide microarray analysis. Biomed Res. 2010;31:169-75 pubmed
    ..These results suggest that a diminution of the intestinal trefoil factor system may be involved in the acceleration of aging in SAM-P6 mice.
  38. Kinzel B, Pikiolek M, Orsini V, Sprunger J, Isken A, Zietzling S, et al. Functional roles of Lgr4 and Lgr5 in embryonic gut, kidney and skin development in mice. Dev Biol. 2014;390:181-90 pubmed publisher
    ..This supports complementary functions of both receptors. Our findings clearly establish the importance of Lgr4 and Lgr5 during embryonic gut, skin and kidney development, with a dominant role of Lgr4...