Gastrin regulates the TFF2 promoter through gastrin-responsivecis-acting elements and multiple signaling pathways

Tu, Shuiping; Alfred, Lawrence J.; Lim, SeonHee; Cui, Guanglin; Dubeykovskaya, Zina; Ai, Wandong; Fleming, John; Takaishi, Shigeo; Wang, Yichen

doi:10.1152/ajpgi.00348.2006

Cited by 36 publications

(30 citation statements)

References 47 publications

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“…In contrast, TFF2 expression was up-regulated by EGF in IEC-6 cells only; whereas TFF1 expression was not altered following EGF treatment. The up-regulation of TFF2 by EGF is in agreement with a previous report using AGS-E cells [47]. The corresponding TFF proteins are well known for their key roles during regeneration and repair of mucous epithelia, particularly by enhancing restitution [4].…”

Section: Egf Induces Expression Of Genes Involved In Emt and Metastasissupporting

confidence: 90%

Modulation of Cell-cell Contacts during Intestinal Restitution In Vitro and Effects of Epidermal Growth Factor (EGF)

Znalesniak¹,

Hoffmann²

2010

Cell Physiol Biochem

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Mucous epithelia represent a major barrier to the outside world and are capable of undergoing rapid repair after injury by cell migration, a process called “restitution”. Here, a sensitive RT-PCR method was applied allowing systematic gene expression analysis of separated stationary and migratory non-transformed IEC-18 and IEC-6 cells after scratch wounding. The focus was on genes related to cell-cell contacts. Furthermore, the effect of epidermal growth factor (EGF) on gene expression was studied. Most of the genes investigated here were down-regulated in migratory cells. Many of the alterations are expected to affect the permeability of tight junctions. Also the nectin-afadin complex of adherens junctions was modulated as well as the expression of both the chemokine receptor CXCR4 and the EGF receptor. Of note, restitution was not accompanied by the epithelial-mesenchymal transition (EMT). EGF treatment severely affected the expression of genes important for cell-cell contact and cell communication such as selected tight junction components, CXCR4, and TFF3. Many of these genes are known to be involved in EMT and metastasis. Of special note, most of the expression changes induced by EGF are in contrast to the changes observed in migratory cells.

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Section: Egf Induces Expression Of Genes Involved In Emt and Metastasissupporting

confidence: 90%

Modulation of Cell-cell Contacts during Intestinal Restitution In Vitro and Effects of Epidermal Growth Factor (EGF)

Znalesniak¹,

Hoffmann²

2010

Cell Physiol Biochem

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“…Antibodies to ␣-tubulin were purchased from Oncogene Science, Inc. (Cambridge, MA). Rabbit anti-TFF2 antibodies to a carboxyl-terminal peptide (16 amino acids) of hTFF2 (which also recognize mTFF2) were developed previously and characterized in our laboratory (31).…”

Section: Methodsmentioning

confidence: 99%

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

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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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“…It was recently shown that expression of TFF2 is enhanced by gastrin, which induces secretion of HCl in the stomach, suggesting a self-protective loop to ensure mucosal protection from the secreted HCl [153].…”

Section: Regulation Of Expressionmentioning

confidence: 99%

The trefoil factor family – small peptides with multiple functionalities

Kjellev¹

2008

Cell. Mol. Life Sci.

234

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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Gastrin regulates the TFF2 promoter through gastrin-responsivecis-acting elements and multiple signaling pathways

Cited by 36 publications

References 47 publications

Modulation of Cell-cell Contacts during Intestinal Restitution <i>In Vitro</i> and Effects of Epidermal Growth Factor (EGF)

Modulation of Cell-cell Contacts during Intestinal Restitution <i>In Vitro</i> and Effects of Epidermal Growth Factor (EGF)

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

The trefoil factor family – small peptides with multiple functionalities

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