Synergistic effects of systemic trefoil factor family 1 (TFF1) peptide and epidermal growth factor in a rat model of colitis

Fitzgerald, Anthony J.; Pu, Mengjia; Marchbank, Tania; Westley, Bruce R.; May, Felicity E. B.; Boyle, J; Yadollahi-Farsani, Masoud; Ghosh, Subrata; Playford, Raymond J.

doi:10.1016/j.peptides.2003.12.022

Cited by 42 publications

(33 citation statements)

References 29 publications

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“…Indeed, Poulsen et al found that while oral treatment with hTFF2 or hTFF3 ameliorated disease, subcutaneous treatment increased the disease score, in agreement with the previous finding by this author that subcutaneous hTFF2 aggravated duodenal ulcers [167]. This led to the suggestion that the markedly lower doses used in [169] may stimulate migration and healing but not affect the viscoelastic properties of mucus, which could potentially have negative effects in the colitis models. Accordingly, we have shown that systemically administered TFF2 and TFF3 specifically binds to cells in the stomach and are transported to the lumen, and that high doses (5 -25 mg/kg) of TFF2 enhance the viscosity of the gastric mucus [158,172,173].…”

Section: Effect Of Tffs In Animal Models Of Diseasesupporting

confidence: 65%

“…As long as the TFFs in vivo mode of action is unclear, the optimal administration route cannot be determined. As in gastric ulceration models, there was a synergistic effect of hTFF1 and EGF [169], and dimeric hTFF1 and hTFF3 were superior to the monomers [164,171]. A marked and equally potent effect of all three trefoils was seen in the DSS model, when the trefoils were expressed locally in the colon by genetically engineered orally administered Lactococcus lactis [174].…”

Section: Effect Of Tffs In Animal Models Of Diseasementioning

confidence: 91%

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The trefoil factor family – small peptides with multiple functionalities

Kjellev¹

2008

Cell. Mol. Life Sci.

235

252

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The trefoil factor family (TFF) comprises a group of small peptides which are highly expressed in tissues containing mucus-producing cells - especially in the mucosa lining the gastrointestinal tract. The peptides seem crucial for epithelial restitution and may work via other pathways than the conventional factors involved in restitution. In vitro studies have shown that the TFFs promote restitution using multiple mechanisms. The peptides also have other functionalities including interactions with the immune system. Moreover, therapeutic effects of the TFFs have been shown in several animal models of gastrointestinal damage. Still it is not clear which of their in vitro properties are involved in the in vivo mode of action. This review describes the TFF family with emphasis on their biological properties and involvement in mucosal protection and repair.

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Section: Effect Of Tffs In Animal Models Of Diseasesupporting

confidence: 65%

Section: Effect Of Tffs In Animal Models Of Diseasementioning

confidence: 91%

The trefoil factor family – small peptides with multiple functionalities

Kjellev¹

2008

Cell. Mol. Life Sci.

235

252

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“…Combined TFF3 and EGF act synergistically with respect to their protective/ motogenic effects in in vivo and in vitro wound healing models [45]. Similar effects were reported for TFF1 and TFF2 pointing again to a natural synergy of TFFs and EGF [35,44,46].…”

Section: Introductionsupporting

confidence: 55%

TFF3 and EGF Induce Different Migration Patterns of Intestinal Epithelial Cells <i>In Vitro</i> and Trigger Increased Internalization of E-cadherin

Dürer

Hartig²,

Bang³

et al. 2007

Cell Physiol Biochem

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Background/Aims: TFF3, a member of the TFF (trefoil factor family) peptides, and epidermal growth factor (EGF) actively support the repair of mucosal barriers, particularly during restitution. The aim of this study was to compare the motogenic effects of TFF3 and EGF. Methods: The influence of recombinant human TFF3 (dimeric form) and EGF on the migration of IEC-18 cells was characterized in an in vitro restitution model (scratch wound assay) with the help of time-lapse video microscopy, morphometry, and immunocytochemistry including confocal laser scanning microscopy. Results: TFF3- and EGF-treated cells re-populated the wounded area via different migration patterns; TFF3 treatment resulted in the formation of continuous sheets of migrating cells with only a few gaps. In contrast, EGF-treated cells formed a network of migrating cells (often with a fibroblast-like morphology) with numerous gaps and only punctual contacts. TFF3 and EGF treatment also changed the localization of E-cadherin indicating endocytotic recycling and/or degradation of E-cadherin. Conclusion: TFF3, in contrast to EGF, enhanced a collective cell migration ensuring a precise coverage of the re-populated area avoiding gaps.

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“…However, the regulation of postnatal intestinal development is known to be influenced by multiple factors modulating intestinal growth, which are also associated with TFF signaling pathways [16,50,51]. Therefore, our following results add additional information to the functional intestinal cellular network that is part of a TFFmediated response.…”

Section: Discussionmentioning

confidence: 65%

Intestinal Expression of TFF and Related Genes During Postnatal Development in a Piglet Probiotic Trial

Scholven

Taras²,

Sharbati

et al. 2009

Cell Physiol Biochem

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Trefoil factor family (TFF) peptides provide protective and reparative effects by enhancing epithelial integrity and promoting mucosal restitution. TFF peptide expression is induced after mucosal damage. These processes are of central physiological relevance during the postnatal intestinal development and are strongly influenced during the weaning period. In piglets, weaning at early maturation stages frequently causes mucosal inflammation. The aim of this study was to evaluate postnatal intestinal TFF expression in a piglet probiotic trial. Low intestinal TFF2 expression was measured at early maturation stages. Weaning, however, was associated with a distinct response of increased TFF2 expression, indicating an important role in enhancing mucosal integrity. In the distal jejunum and ileum weaning could as well be associated with increased TFF3 mRNA levels. Differential TFF1 expression was not detected. Furthermore, TFF2 localization studies in different intestinal loci were performed by means of immunohistochemistry. Expression of selected genes (TGFA, EGFR, Cox-2) known to promote TFF signaling showed differential expression pattern as well, thereby providing further functional background. Furthermore, the expression patterns of EGFR observed in this study contribute to an advanced view of previous findings of EGFR regulation mainly obtained in rodents. An upregulated EGFR expression during early postnatal development suggests a local relevance to porcine intestinal maturation. However, a feed supplementation with the probiotic strain Enterococcus faecium did not influence TFF expression.

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Synergistic effects of systemic trefoil factor family 1 (TFF1) peptide and epidermal growth factor in a rat model of colitis

Cited by 42 publications

References 29 publications

The trefoil factor family – small peptides with multiple functionalities

The trefoil factor family – small peptides with multiple functionalities

TFF3 and EGF Induce Different Migration Patterns of Intestinal Epithelial Cells <i>In Vitro</i> and Trigger Increased Internalization of E-cadherin

Intestinal Expression of TFF and Related Genes During Postnatal Development in a Piglet Probiotic Trial

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