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

• Thus, NEP has important roles in regulating basal microvascular permeability by degrading SP and BK, and may regulate blood pressure set point through a mechanism that is independent of SP, BK and NO [3].
• Trefoil factor family 2 (TFF2), also known as spasmolytic polypeptide, is a member of the trefoil family of peptides and is expressed primarily in the mucous neck cells of the gastric mucosa [11].
• Spasmolytic polypeptide expressing metaplasia to preneoplasia in H. felis-infected mice [12].
• In addition, the C57BL/6 mouse showed a marked loss of parietal and chief cells, along with a marked expansion of an aberrant gastric mucous cell lineage that stained positive for spasmolytic polypeptide [13].
• Using in situ hybridization, we show that although coexpressed in the fundus, the antrum and the antrum-pyloric regions of the stomach, the mouse pS2 and mSP genes exhibit distinct and complementary cellular patterns of expression [14].

Chemical compound and disease context of Tff2

• DMP-777 elicits a rapid loss of parietal cells followed by the emergence of foveolar hyperplasia and spasmolytic polypeptide (SP)-expressing metaplasia (SPEM) [1].
• 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 [15].
• Because METH augments striatal substance P (SP) levels, we hypothesized that this neuropeptide plays a role in methamphetamine-induced toxicity and neural damage in the striatum [16].
• Twenty-four hours after instillation of LPS or SP, bladder inflammation was characterized by edema and leukocytic infiltration of the bladder wall [17].
• Although glutamate is co-localized with SP in dorsal root ganglion neurons, its role in nociceptive processing is uncertain [18].

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

• SP expression in airway-specific and overall vagal sensory neurons of the jugular and nodose ganglion complex was analysed using retrograde neuronal tracing in combination with immunohistochemistry [23].
• Preprotachykinin A (PPT-A) mRNA, the precursor for SP, was quantified in lung tissue by real-time PCR [23].
• These results suggest that a single and repeated immobilization stress differentially affects such nociceptive processing induced by formalin, SP, glutamate and pro-inflammatory cytokines in different manners [28].
• However, a difference in SP release evoked in the dorsal horn by electrical stimulation of the dorsal roots or capsaicin application was not observed [29].
• An intradermal injection of SP (10-135 microgram site-1) into the rostral back of the ICR mouse dose-dependently produced scratching of the injected site [30].

References