Transcriptional control of TFF3 (intestinal trefoil factor) via promoter binding sites for the nuclear factor κB and C/EBPβ

Baus-Lončar, Mirela; Al-azzeh, Ezzal-din; Romańska, Hanna; Lalani, El–Nasir; Stamp, Gordon; Blin, Nikolaus; Kayademir, Tuncay

doi:10.1016/j.peptides.2003.11.019

Cited by 25 publications

(19 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TFFs are GI factors that allow the healthy mucosa to restrain inflammation and live harmoniously with its abundant flora. Their expression is modulated by pro-and anti-inflammatory cytokines [22][23][24][25]. Cytokines such as IL-1β and IL-6 down-regulate TFF genes expression by transcriptional repression in GI cells.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cytokine Regulation of the Trefoil Factor Family Binding Protein GKN2 (GDDR/TFIZ1/blottin) in Human Gastrointestinal Epithelial Cells

Baus-Lončar

Lubka

Pusch

et al. 2007

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

Trefoil factor family (TFF) peptides are major secretory products of mucous epithelia and play a multifunctional role in cytoprotection, apoptosis, and immune response. Recently, a TFF2-binding protein was discovered in mice and named blottin. It is down-regulated in gastric cancer (GDDR), abundant in human gastric surface (TFIZ1) and its similarity to gastrokine-1 led to the gene’s name GKN2. To investigate the mode of GKN2 regulation activity of a luciferase reporter gene, controlled by the GKN2 promoter, was monitored upon treatment with various pro-inflammatory (TNF-α, IL-1β, IL-6, IFN-γ) and anti-inflammatory (TGF-β1) cytokines using gastric (AGS, KATO III) and colonic (HT-29) cell lines. To assess the direct role of transcription factors (NFĸB, HNF-3β, hGATA6) in regulating GKN2 we performed transient co-transfection of their expression plasmids and the reporter gene construct. GKN2 gene was down-regulated by pro-inflammatory cytokines in all tested cell lines while up-regulated by TGF-β1 only in the colonic cell line. GKN2 expression was significantly reduced in both gastric adenocarcinoma cell lines by the active form of NFĸB transcription factor, whereas in the colonic cell line an up-regulation was noticed. Down-regulation by IL-6 was mediated by C/EBPβ transcription factor in case of HT-29 but not of KATO III cells. We conclude that the regulation of GKN2 parallels that of TFF genes, indicating that together they may play an important role in maintaining the homeostasis of the gastrointestinal tract.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Trefoil peptides co-operate in the protection of the mucosal barrier and are regulated by both pro-inflammatory [22] and anti-inflammatory [23][24][25] cytokine expression. A number of regulatory peptides including transforming growth factor (TGF)-β, interleukin (IL)-1β, and interferon (IFN)-γ stimulate restitution of GI epithelia.…”

Section: Introductionmentioning

confidence: 99%

Cytokine Regulation of the Trefoil Factor Family Binding Protein GKN2 (GDDR/TFIZ1/blottin) in Human Gastrointestinal Epithelial Cells

Baus-Lončar

Lubka

Pusch

et al. 2007

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

show abstract

“…The HNF3/FKH and NF-κB binding sites have been reported as an important motif for the expression of the TFF3 gene (28,29). Hypomethylation of a HpaII site in TFF3 5′ upstream of 129 strain suggests association with tissue-specific expression of the mouse TFF3 gene (30), although this site is within 129 strainspecific insertion of a B1 repetitive element and far from the HNF3/FKH and NF-κB binding sites.…”

Section: Discussionmentioning

confidence: 99%

Frequent trefoil factor 3 (TFF3) overexpression and promoter hypomethylation in mouse and human hepatocellular carcinomas

Okada

Kimura

Tan³

et al. 2005

Int J Oncol

View full text Add to dashboard Cite

Expression profiling analysis revealed ectopic high expression of mouse TFF3 in non-tumor liver tissues from the hepatocellular carcinoma (HCC) susceptible PWK/Rbrc strain. TFF3 is a member of the trefoil factor family peptides, which are small secreted proteins regulating mucosal regeneration and repair, and which are overexpressed during inflammatory processes and cancer progression. We, therefore, analyzed the TFF3 expression extensively in mouse and human HCCs. Expression of the mouse TFF3 gene was significantly increased in 6 out of 7 HCCs from a PWK spontaneous tumor model and in all 7 HCCs from an SV40T antigen-induced transgenic MT-D2C57BL/6 model. In humans, 8 of 20 HCCs (40%) had overexpression of TFF3 in both mRNA level and protein level. We then analyzed DNA methylation patterns of the TFF3 promoter region to evaluate expression regulation of promoter methylation. In mouse HCCs, we demonstrated that two CpGs, at positions −992 and +109, were hypomethylated in 13 of 14 mouse HCCs. In human HCCs, hypomethylation at CpG −260 was associated with TFF3 overexpression (p=0.04). These results indicate that TFF3 overexpression may be a critical process in mouse and human hepatocellular carcinogenesis, and the specific promoter CpG hypomethylation may be one of the regulation mechanisms of TFF3 overexpression in HCCs.

show abstract

“…In modulating mucosal immune responses at the level of leukocyte recruitment [12] and tissue repair functions, TFFs have a major impact on maintenance of healthy mucosal surfaces. They are regulated by both pro-inflammatory [13] and anti-inflammatory cytokines [14]. One of the important local cytokines likely regulating TFF2 and TFF3 during mucosal repair is the transforming growth factor-alpha (TGFA) [15,16].…”

Section: Introductionmentioning

confidence: 99%

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

Scholven

Taras²,

Sharbati

et al. 2009

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Transcriptional control of TFF3 (intestinal trefoil factor) via promoter binding sites for the nuclear factor κB and C/EBPβ

Cited by 25 publications

References 27 publications

Cytokine Regulation of the Trefoil Factor Family Binding Protein GKN2 (GDDR/TFIZ1/blottin) in Human Gastrointestinal Epithelial Cells

Cytokine Regulation of the Trefoil Factor Family Binding Protein GKN2 (GDDR/TFIZ1/blottin) in Human Gastrointestinal Epithelial Cells

Frequent trefoil factor 3 (TFF3) overexpression and promoter hypomethylation in mouse and human hepatocellular carcinomas

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

Contact Info

Product

Resources

About