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Gene Review

Tff2  -  trefoil factor 2 (spasmolytic protein 1)

Mus musculus

Synonyms: SP, Sml1, Sp, Spasmolytic polypeptide, Trefoil factor 2, ...
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Disease relevance of Tff2

  • These results suggest that SP/TFF2 does not impact on the development of metaplasia after the induction of parietal cell loss [1].
  • PURPOSE: To determine the effects of blocking substance P (SP) interactions with its major receptor (NK1-R) using the antagonist spantide I in susceptible mice infected with Pseudomonas aeruginosa [2].
  • Substance P (SP) and bradykinin (BK) mediate extravasation and cause hypotension [3].
  • Thus we conclude that RP 67580, a SP antagonist, belongs to a class of drugs that may be useful in the management of various clinical pathologies where pain and neurogenic inflammation are involved [4].
  • Within the granuloma SP can modulate IFN-gamma production through interaction with a substance P-like receptor [5].

Psychiatry related information on Tff2

  • More recently, the neuropeptide substance P (SP) and its receptor (the neurokinin-1 receptor [NK1R]) have been implicated in the pathophysiology of affective disorders, including depression [6].
  • In addition, SP may modulate the release of nigrostriatal monoamines, which have also been linked with avoidance learning [7].
  • BACKGROUND: Atopic dermatitis (AD) can be exacerbated or induced in genetically predisposed individuals by psychological stress, which causes the release of substance P (SP) [8].
  • Finally, in an experimental in vivo lung cancer model, SP therapy significantly reduced the numbers of lung tumors, increased animal survival, and activated pulmonary immune defense mechanisms [9].
  • This finding may have clinical implications for Rett syndrome in which SP levels along with other neuromodulators are decreased in the brainstem [10].

High impact information on Tff2


Chemical compound and disease context of Tff2


Biological context of Tff2

  • In conclusion, SP content and NK1r expression are noticeably different in c-kit mutants with respect to wild type mice, and probably causing an anomalous tachykininergic control of intestinal motility [19].
  • SR 140333 antagonized the salivation induced by SP, [Sar9, Met(O2)11]-SP and septide in rats (ID50 = 0.13, 0.18 and 0.09 mg/kg i.p., respectively) [20].
  • PMN chemotaxis was induced by SP and other neuropeptides in vitro, but was not affected by spantide I. mRNA for neurokinin-1-receptor-1 (NK-1R) was detected in the normal and infected corneas and on macrophages (Mphis), but not on PMNs (unstimulated or stimulated with endotoxin [LPS]) [2].
  • The characteristics of SP(1-7) binding sites are consistent with those expected for an SP N-terminal receptor [21].
  • Conversely, deprivation of Sp proteins by transfection of decoy Sp1 oligonucleotide or blockade of Sp1 binding with mithramycin A inhibited c-met expression [22].

Anatomical context of Tff2

  • OBJECTIVE: The aim of this study was to investigate the effects of stress alone or in combination with allergic airway inflammation on SP expression in sensory neurons innervating the mouse airways [23].
  • The richness in SP-IR nerve fibers and the NK1r-IR distribution in the neurons, similar to that of activated cells, might be attempts to compensate for the SP preferred receptor absence at the ICC-DMP [19].
  • SP and ITF levels in tissue fell within 48 h of ulceration (P < 0.05), but secretion into gastric juice was unchanged [24].
  • These results suggest that mast cells undergo maturation under the influence of fibroblasts, acquiring the responsiveness to SP with Ca(2+) signals and predominantly ERK-MAP kinase [25].
  • Substance P (SP) selectively activates mast cells that reside in connective tissues [25].

Associations of Tff2 with chemical compounds

  • BACKGROUND: Tachykinins-like substance P (SP) have been shown to play an important role in initiating and perpetuating airway inflammation [23].
  • Associated with enhanced neuronal SP expression, a significantly higher number of leucocytes were found in the BAL following allergen exposure [23].
  • As in wild-type mice, treatment with DMP-777 for 7 days did elicit SPEM in SP/TFF2-deficient mice [1].
  • These results suggest that atropine-sensitive phasic contraction is mainly mediated via the M(3) receptor, and SP-mediated sustained contraction is negatively regulated by the M(2) receptor at a presynaptic level [26].
  • These results suggest that i.t.-administered S-(+)-fenfluramine releases SP through the activation of 5-HT2 receptors subsequent to 5-HT release, and, as a result, produces nociceptive behavior [27].

Other interactions of Tff2

  • 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) [24].
  • The induction of SP and ITF expression in the latter stages of injury repair has a TGF-alpha-dependent component and suggests a role for these peptides in gastric differentiation and cell positioning [24].

Analytical, diagnostic and therapeutic context of Tff2


  1. Altered metaplastic response of waved-2 EGF receptor mutant mice to acute oxyntic atrophy. Ogawa, M., Nomura, S., Varro, A., Wang, T.C., Goldenring, J.R. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  2. Spantide I Decreases Type I Cytokines, Enhances IL-10, and Reduces Corneal Perforation in Susceptible Mice after Pseudomonas aeruginosa Infection. Hazlett, L.D., McClellan, S.A., Barrett, R.P., Liu, J., Zhang, Y., Lighvani, S. Invest. Ophthalmol. Vis. Sci. (2007) [Pubmed]
  3. The control of microvascular permeability and blood pressure by neutral endopeptidase. Lu, B., Figini, M., Emanueli, C., Geppetti, P., Grady, E.F., Gerard, N.P., Ansell, J., Payan, D.G., Gerard, C., Bunnett, N. Nat. Med. (1997) [Pubmed]
  4. Pharmacological properties of a potent and selective nonpeptide substance P antagonist. Garret, C., Carruette, A., Fardin, V., Moussaoui, S., Peyronel, J.F., Blanchard, J.C., Laduron, P.M. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  5. Molecular evidence that granuloma T lymphocytes in murine schistosomiasis mansoni express an authentic substance P (NK-1) receptor. Cook, G.A., Elliott, D., Metwali, A., Blum, A.M., Sandor, M., Lynch, R., Weinstock, J.V. J. Immunol. (1994) [Pubmed]
  6. Behavioral and physiologic effects of genetic or pharmacologic inactivation of the substance P receptor (NK1). Santarelli, L., Gobbi, G., Blier, P., Hen, R. The Journal of clinical psychiatry. (2002) [Pubmed]
  7. Nigral 5-HT and substance P-induced enhancement of passive avoidance retention. Pelleymounter, M.A., Schlesinger, K., Wehner, J., Hall, M.E., Stewart, J.M. Behav. Brain Res. (1988) [Pubmed]
  8. Role of substance P in an NC/Nga mouse model of atopic dermatitis-like disease. Ohmura, T., Tsunenari, I., Hayashi, T., Satoh, Y., Konomi, A., Nanri, H., Kawachi, M., Morikawa, M., Kadota, T., Satoh, H. Int. Arch. Allergy Immunol. (2004) [Pubmed]
  9. Aerosolized substance P protects against cigarette-induced lung damage and tumor development. Harris, D.T., Witten, M. Cell. Mol. Biol. (Noisy-le-grand) (2003) [Pubmed]
  10. Substance P-mediated modulation of pacemaker properties in the mammalian respiratory network. Peña, F., Ramirez, J.M. J. Neurosci. (2004) [Pubmed]
  11. TFF2/SP-deficient mice show decreased gastric proliferation, increased acid secretion, and increased susceptibility to NSAID injury. Farrell, J.J., Taupin, D., Koh, T.J., Chen, D., Zhao, C.M., Podolsky, D.K., Wang, T.C. J. Clin. Invest. (2002) [Pubmed]
  12. Spasmolytic polypeptide expressing metaplasia to preneoplasia in H. felis-infected mice. Nomura, S., Baxter, T., Yamaguchi, H., Leys, C., Vartapetian, A.B., Fox, J.G., Lee, J.R., Wang, T.C., Goldenring, J.R. Gastroenterology (2004) [Pubmed]
  13. Mice lacking secretory phospholipase A2 show altered apoptosis and differentiation with Helicobacter felis infection. Wang, T.C., Goldenring, J.R., Dangler, C., Ito, S., Mueller, A., Jeon, W.K., Koh, T.J., Fox, J.G. Gastroenterology (1998) [Pubmed]
  14. The mouse one P-domain (pS2) and two P-domain (mSP) genes exhibit distinct patterns of expression. Lefebvre, O., Wolf, C., Kédinger, M., Chenard, M.P., Tomasetto, C., Chambon, P., Rio, M.C. J. Cell Biol. (1993) [Pubmed]
  15. Hyperplastic gastric tumors with spasmolytic polypeptide-expressing metaplasia caused by tumor necrosis factor-alpha-dependent inflammation in cyclooxygenase-2/microsomal prostaglandin E synthase-1 transgenic mice. Oshima, M., Oshima, H., Matsunaga, A., Taketo, M.M. Cancer Res. (2005) [Pubmed]
  16. Neurokinin-1 (NK-1) receptor antagonists abrogate methamphetamine-induced striatal dopaminergic neurotoxicity in the murine brain. Yu, J., Cadet, J.L., Angulo, J.A. J. Neurochem. (2002) [Pubmed]
  17. LPS-sensory peptide communication in experimental cystitis. Saban, M.R., Saban, R., Hammond, T.G., Haak-Frendscho, M., Steinberg, H., Tengowski, M.W., Bjorling, D.E. Am. J. Physiol. Renal Physiol. (2002) [Pubmed]
  18. Neurokinin and NMDA antagonists (but not a kainic acid antagonist) are antinociceptive in the mouse formalin model. Murray, C.W., Cowan, A., Larson, A.A. Pain (1991) [Pubmed]
  19. Substance P and Neurokinin 1 receptor - expression is affected in the ileum of mice with mutation in the W locus. Faussone-Pellegrini, M.S., Vannucchi, M.G. J. Cell. Mol. Med. (2006) [Pubmed]
  20. Neuropharmacological characterization of SR 140333, a non peptide antagonist of NK1 receptors. Jung, M., Calassi, R., Maruani, J., Barnouin, M.C., Souilhac, J., Poncelet, M., Gueudet, C., Emonds-Alt, X., Soubrié, P., Brelière, J.C. Neuropharmacology (1994) [Pubmed]
  21. Specific binding of substance P aminoterminal heptapeptide [SP(1-7)] to mouse brain and spinal cord membranes. Igwe, O.J., Kim, D.C., Seybold, V.S., Larson, A.A. J. Neurosci. (1990) [Pubmed]
  22. Sp1 and Sp3 transcription factors synergistically regulate HGF receptor gene expression in kidney. Zhang, X., Li, Y., Dai, C., Yang, J., Mundel, P., Liu, Y. Am. J. Physiol. Renal Physiol. (2003) [Pubmed]
  23. Stress induces substance P in vagal sensory neurons innervating the mouse airways. Joachim, R.A., Cifuentes, L.B., Sagach, V., Quarcoo, D., Hagen, E., Arck, P.C., Fischer, A., Klapp, B.F., Dinh, Q.T. Clin. Exp. Allergy (2006) [Pubmed]
  24. Temporal expression of trefoil peptides in the TGF-alpha knockout mouse after gastric ulceration. Cook, G.A., Yeomans, N.D., Giraud, A.S. Am. J. Physiol. (1997) [Pubmed]
  25. Bone marrow derived mast cell acquire responsiveness to substance P with Ca(2+) signals and release of leukotriene B(4) via mitogen-activated protein kinase. Okabe, T., Hide, M., Hiragun, T., Morita, E., Koro, O., Yamamoto, S. J. Neuroimmunol. (2006) [Pubmed]
  26. M2 and M3 muscarinic receptors are involved in enteric nerve-mediated contraction of the mouse ileum: findings obtained with muscarinic-receptor knockout mouse. Takeuchi, T., Tanaka, K., Nakajima, H., Matsui, M., Azuma, Y.T. Am. J. Physiol. Gastrointest. Liver Physiol. (2007) [Pubmed]
  27. S-(+)-fenfluramine-induced nociceptive behavior in mice: Involvement of interactions between spinal serotonin and substance P systems. Tan-No, K., Takahashi, K., Shimoda, M., Sugawara, M., Nakagawasai, O., Niijima, F., Sato, T., Satoh, S., Tadano, T. Neuropeptides (2007) [Pubmed]
  28. Changes in pain behavior induced by formalin, substance P, glutamate and pro-inflammatory cytokines in immobilization-induced stress mouse model. Seo, Y.J., Kwon, M.S., Shim, E.J., Park, S.H., Choi, O.S., Suh, H.W. Brain Res. Bull. (2006) [Pubmed]
  29. Basal and activity-induced release of substance P from primary afferent fibres in NK1 receptor knockout mice: evidence for negative feedback. Lever, I.J., Grant, A.D., Pezet, S., Gerard, N.P., Brain, S.D., Malcangio, M. Neuropharmacology (2003) [Pubmed]
  30. Substance P induction of itch-associated response mediated by cutaneous NK1 tachykinin receptors in mice. Andoh, T., Nagasawa, T., Satoh, M., Kuraishi, Y. J. Pharmacol. Exp. Ther. (1998) [Pubmed]
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