Salivary trefoil factor 3 enhances migration of oral keratinocytes

Storesund, Trond; Hayashi, Kozaburo; Kolltveit, Kristin M.; Bryne, Magne; Schenck, Karl

doi:10.1111/j.1600-0722.2007.00516.x

Cited by 58 publications

(53 citation statements)

References 35 publications

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“…ITF have been reported to promote cell proliferation and migration of epithelial cells in some studies (7,17,18), and our experiments indicated that ITF promote proliferation and migration of GES-1 cell in vitro. To verify whether Akt signaling pathway participated in this stimulatory effect, CCK-8 assays and transwell migration assays were performed.…”

Section: Activated Akt Signaling Is Required For Itf-induced Ges-1 Cesupporting

confidence: 49%

Intestinal trefoil factor activates the PI3K/Akt signaling pathway to protect gastric mucosal epithelium from damage

Sun

Yang

et al. 2014

International Journal of Oncology

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Abstract.Intestinal trefoil factor (ITF, also named as trefoil factor 3, TFF3) is a member of the TFF-domain peptide family, which plays an essential role in the regulation of cell survival, cell migration and maintains mucosal epithelial integrity in the gastrointestinal tract. However, the underlying mechanisms and associated molecules remain unclear. The aim of this study was to explore the protective effects of ITF on gastric mucosal epithelium injury and its possible molecular mechanisms of action. In the present study, we show that ITF was able to promote the proliferation and migration of GES-1 cells via a mechanism that involves the PI3K/Akt signaling pathway. Western blot results indicated that ITF induced a dose-and time-dependent increase in the Akt signaling pathway. ITF also plays an essential role in the restitution of GES-1 cell damage induced by lipopolysaccharide (LPS). LPS induced the apoptosis of GES-1 cells, decreased cell viability significantly (P<0.01) and led to epithelial tight junction damage, which is attenuated via ITF treatment. The protective effect of ITF on the integrity of GES-1 was abrogated by inhibition of the PI3K/Akt pathway. Taken together, our results demonstrate that ITF promotes the proliferation and migration of gastric mucosal epithelial cells and preserves gastric mucosal epithelial integrity after damage is mediated by activation of the PI3K/Akt signaling pathway. This study suggested that the PI3K/Akt pathway could act as a key intracellular pathway in the gastric mucosal epithelium that may serve as a therapeutic target to preserve epithelial integrity during injury.

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Section: Activated Akt Signaling Is Required For Itf-induced Ges-1 Cesupporting

confidence: 49%

Intestinal trefoil factor activates the PI3K/Akt signaling pathway to protect gastric mucosal epithelium from damage

Sun

Yang

et al. 2014

International Journal of Oncology

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“…That these effects could reversed by a β-AR antagonist, but not an α 2 -AR-antagonist, suggests that the migratory effects are mediated by the β-AR, and since the β 2 -AR is the only β-AR expressed, it is likely that the effects are mediated by the β 2 -AR. The catecholamine agonists also decrease the activity of the pro-migratory ERK and p38 MAPK, kinases required for epithelial cell migration (McCawley et al, 1999;Fitsialos et al, 2007;Storesund et al, 2008;Shi et al, 2009;Sivamani et al, 2009b) and convert HOK from a migratory to a stationary phenotype. Additionally, the HOK themselves can generate catecholamine ligands.…”

Section: Discussionmentioning

confidence: 99%

Adrenergic Signaling in Human Oral Keratinocytes and Wound Repair

et al. 2010

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A supplemental appendix to this article is published electronically only at http://jdr.sagepub.com/supplemental. ABSTRACT Catecholamines are present in saliva, but their influence on oral epithelium is not understood. Because psychological stress increases salivary catecholamines and impairs oral mucosal wound healing, we sought to determine if epithelial adrenergic signaling could link these two findings. We found that cultured human oral keratinocytes (HOK) express the α 2B -and β 2 -adrenergic receptors (ARs). Exposure of HOK to either epinephrine or the β-AR agonist, isoproterenol, reduced migratory speed and decreased in vitro scratch wound healing. Incubation with the β-AR antagonist timolol reversed the catecholamine-induced effects, indicating that the observed response is mediated by β-AR. Epinephrine treatment decreased phosphorylation of the mitogen-activated protein kinases (MAPK) ERK1/2 and p38; these decreases were also reversed with timolol. Cultured HOK express enzymes of the epinephrine synthetic pathway, and generate epinephrine. These findings demonstrate that stress-induced elevations of salivary catecholamines signal through MAPK pathways, and result in impaired oral keratinocyte migration required for healing.

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“…The TFF3 protein also activates STAT3 signaling in human colorectal cancer cells, thus providing cells with invasion potential (20). TFF3 treatment leads to EGF receptor activation and ␤-catenin phosphoryla-tion in HT-29 cells (21) and to transient phosphorylation of ERK1/2 in oral keratinocytes (22). With respect to TFF2, recombinant peptide enhances the migration of human bronchial epithelial cell line BEAS-2B (4).…”

mentioning

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

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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Salivary trefoil factor 3 enhances migration of oral keratinocytes

Cited by 58 publications

References 35 publications

Intestinal trefoil factor activates the PI3K/Akt signaling pathway to protect gastric mucosal epithelium from damage

Intestinal trefoil factor activates the PI3K/Akt signaling pathway to protect gastric mucosal epithelium from damage

Adrenergic Signaling in Human Oral Keratinocytes and Wound Repair

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

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