Trefoil factors

Baus-Lončar, Mirela; Kayademir, Tuncay; Takaishi, Shigeo; Wang, Yichen

doi:10.1007/s00018-005-5483-7

Cited by 63 publications

(35 citation statements)

References 74 publications

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“…TFF peptides have also been shown in vitro to enhance cell migration (motogenic effect) and cell scattering [32], which both are effects that support the process of mucosal restitution. Recently, association between TFFs and the immune system has been demonstrated [25, 26]. …”

Section: Discussionmentioning

confidence: 99%

“…In support of the protective and reparative functions of TFFs in the gastrointestinal tract are studies showing upregulation of the expression of all three TFFs at sites of damage in conditions such as inflammatory bowel disease (IBD) or peptic ulcer [23, 24]. In addition, an increasing body of evidence connects TFFs with a possible role in immunoregulation as demonstrated for TFF2 [25, 26]. …”

Section: Introductionmentioning

confidence: 99%

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Serum Trefoil Factors in Patients with Inflammatory Bowel Disease

Grønbæk¹,

Vestergaard

Hey³

et al. 2006

Digestion

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Background: Trefoil factors (TFF1–3) play a critical role in mucosal protection and repair in the gastrointestinal tract. The aims of the present study were to examine associations between serum TFF1–3 and clinical and biochemical markers reflecting disease activity and to examine changes in TFF1–3 in patients with inflammatory bowel disease (IBD) before and during high-dose prednisolone treatment and tapering.Methods: Serum concentrations of TFF1–3 were quantified in 48 ulcerative colitis (UC) and 50 Crohn’s disease (CD) patients with little or moderate activity. Additionally, serum TFF concentrations were determined in patients with severe activity in colon IBD (4 UC and 6 CD) before and during prednisolone treatment with 7 healthy subjects as controls. Results: Median concentrations of TFF1, TFF2, and TFF3 were significantly increased in IBD patients compared with healthy controls (p < 0.01). TFF3 concentrations correlated with clinical and biochemical parameters of disease activity in UC patients. In addition, a trend towards reduction in TFF concentrations during treatment with prednisolone and concomitant clinical and biochemical remission was observed. Conclusions: The present data support the concept that trefoil peptides are upregulated and may play a role in IBD mucosal protection and repair. In UC patients, TFF3 levels were increased in active disease levels correlated with disease activity indices. Due to a large variation, serum TFFs are not a potential marker for disease activity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Serum Trefoil Factors in Patients with Inflammatory Bowel Disease

Grønbæk¹,

Vestergaard

Hey³

et al. 2006

Digestion

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“…2ϩ Signaling in Jurkat Cells-We and others have previously demonstrated TFF2 mRNA expression in the secondary mouse lymphoid organs, namely the spleen and thymus (25)(26)(27). To evaluate possible TFF2 regulation in splenocytes by mitogens, we stimulated mouse splenocytes with T cell and B cell mitogens, concanavalin A and lipopolysaccharide, respectively.…”

Section: Tff2 Attenuates Sdf-1␣/cxcr4-mediated Chemotaxis and Camentioning

confidence: 99%

“…In addition, TFF2 was detected in rat lymphoid tissues (spleen, lymph nodes, and bone marrow) (25). Recently we and others found TFF2 mRNA expression in primary and secondary lymphopoietic organs (26,27). These data suggest that TFF2 may play some function in the immune system.…”

mentioning

confidence: 92%

Secreted Trefoil Factor 2 Activates the CXCR4 Receptor in Epithelial and Lymphocytic Cancer Cell Lines

Dubeykovskaya

Dubeykovskiy

Solal-Cohen

et al. 2009

Journal of Biological Chemistry

106

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The secreted trefoil factor family 2 (TFF2) protein contributes to the protection of the gastrointestinal mucosa from injury by strengthening and stabilizing mucin gels, stimulating epithelial restitution, and restraining the associated inflammation. Although trefoil factors have been shown to activate signaling pathways, no cell surface receptor has been directly linked to trefoil peptide signaling. Here we demonstrate the ability of TFF2 peptide to activate signaling via the CXCR4 chemokine receptor in cancer cell lines. We found that both mouse and human TFF2 proteins (at ϳ0.5 M) activate Ca 2؉ signaling in lymphoblastic Jurkat cells that could be abrogated by receptor desensitization (with SDF-1␣) or pretreatment with the specific antagonist AMD3100 or an anti-CXCR4 antibody. TFF2 pretreatment of Jurkat cells decreased Ca 2؉ rise and chemotactic response to SDF-1␣. In addition, the CXCR4-negative gastric epithelial cell line AGS became highly responsive to TFF2 treatment upon expression of the CXCR4 receptor. TFF2-induced activation of mitogen-activated protein kinases in gastric and pancreatic cancer cells, KATO III and AsPC-1, respectively, was also dependent on the presence of the CXCR4 receptor. Finally we demonstrate a distinct proliferative effect of TFF2 protein on an AGS gastric cancer cell line that expresses CXCR4. Overall these data identify CXCR4 as a bona fide signaling receptor for TFF2 and suggest a mechanism through which TFF2 may modulate immune and tumorigenic responses in vivo.

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“…Tff2 KO mice show an altered expression of genes implicated in immune regulation [35] and their immune cells are hyperresponsive to IL-1β stimulation [30]. …”

Section: Introductionmentioning

confidence: 99%

Porcine Gastric TFF2 is a Mucus Constituent and Differs from Pancreatic TFF2

Stürmer

Müller

Hanisch

et al. 2014

Cell Physiol Biochem

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Background/Aims: TFF2 is a secretory peptide (106 amino acid residues) of the gastric mucosa, the porcine exocrine pancreas as well as immune cells and the CNS. It was the aim of this study to compare gastric and pancreatic TFF2. Methods: TFF2 was purified from the porcine stomach and pancreas, respectively, by size-exclusion and anion-exchange chromatography and then analyzed by Western blots as well as mass spectrometry. Results: Gastric and pancreatic TFF2 differed markedly, i.e. gastric TFF2 was exclusively associated with the high molecular mass mucus fraction, whereas pancreatic TFF2 appeared as a low molecular mass product. Unexpectedly, the latter predominantly formed a non-covalently linked homodimer resistant to boiling SDS. In contrast, gastric TFF2 is an integral mucus constituent predominantly binding to the mucin MUC6 in a non-covalent fashion. Conclusion: The non-covalent interaction of TFF2 with the mucin MUC6 is typical of a "link peptide" which is perfectly suited to assemble and stabilize the laminated structure of gastric mucus and to modulate its rheological properties.

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Trefoil factors

Cited by 63 publications

References 74 publications

Serum Trefoil Factors in Patients with Inflammatory Bowel Disease

Serum Trefoil Factors in Patients with Inflammatory Bowel Disease

Secreted Trefoil Factor 2 Activates the CXCR4 Receptor in Epithelial and Lymphocytic Cancer Cell Lines

Porcine Gastric TFF2 is a Mucus Constituent and Differs from Pancreatic TFF2

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