Peroxisome proliferator-activated receptor γ (PPARγ) regulates trefoil factor family 2 (TFF2) expression in gastric epithelial cells

Shimada, Tadahito; Fujii, Yoshiko; Koike, Toshiyuki; Tabei, Kyoko; Namatame, Takashi; Yamagata, Michiko; Tajima, Akihiro; Yoneda, Masashi; Terano, Akira; Hiraishi, Hideyuki

doi:10.1016/j.biocel.2006.10.015

Cited by 14 publications

(16 citation statements)

References 45 publications

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“…These results are in line with studies showing that Tff3-null mice challenged with 2.5% of DSS have impaired mucosal healing and are more sensitive to the injurious effects of DSS than the wild type (7). Also, both in vitro and in vivo studies have shown that PPARg ligands such as troglitazone and prostaglandins, and nonsteroidal antiinflammatory drugs such as aspirin upregulate TFF2 expression (19,48,49), which leads to inhibition of DSS-induced colitis and azoxymethane-induced colon carcinoma (50). No evidence of TFF3 regulation by PPARg has been indicated, making this study the first one to our knowledge suggesting this link.…”

Section: Discussionsupporting

confidence: 90%

“…No evidence of TFF3 regulation by PPARg has been indicated, making this study the first one to our knowledge suggesting this link. The presence of potential PPARg binding sites in the promoter sequence of TFF3 and a study showing PPARg-dependent regulation of TFF2 in gastric epithelial cells through a functional PPRE in TFF2 (19) suggest the involvement of PPARg in the regulation of TFF3. The regulation of TFF3 by PPARg may involve other mucusprotective components like mucins, which can have an additional role in maintaining the homeostasis in the gastrointestinal mucosa (Fig.…”

Section: Discussionmentioning

confidence: 95%

“…Although PPARg regulates a number of antiinflammatory pathways, little is known about how this transcription factor affects the more recently discovered TFF. Studies in gastric epithelial cells have suggested the presence of a PPARg-binding site in the TFF2 gene (19) Here, we examined the potential therapeutic effect of dietary CLA in an experimental model of IBD and explored the role of PPARg and TFF3 in the antiinflammatory actions of CLA.…”

Section: Introductionmentioning

confidence: 98%

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Dietary Conjugated Linoleic Acid Activates PPARγ and the Intestinal Trefoil Factor in SW480 Cells and Mice with Dextran Sulfate Sodium-Induced Colitis3

Borniquel

Jädert

Lundberg

2012

The Journal of Nutrition

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A central event in inflammatory bowel disease is the disruption of the mucosal homeostasis. Trefoil peptides [(TFF)] are emerging as key mediators in the defense and repair of the gastrointestinal mucosa. Here, we demonstrate induction of TFF by CLA with therapeutic antiinflammatory effects in a mouse model of inflammatory bowel disease. SW480 cells were treated with linoleic acid or CLA (0-2.5 μmol/L) in the absence or presence of the PPARγ inhibitor GW9662. Cells treated with CLA showed an upregulation of the intestinal trefoil factor, which was prevented by pretreatment with GW9662. Dextran sulfate sodium (2%) was used to induce colitis in mice and they were simultaneously fed with a standard or a CLA-supplemented (100 mg · kg(-1) · d(-1)) diet for 7 d. The CLA-enriched diet prevented the colon shortening induced by DSS and markedly reduced the disease activity index and the colonic expression of inducible NO synthase and NF-κB. Immunohistochemistry revealed an increase in PPARγ and TFF3 expression after CLA administration. Altogether, these results indicate that dietary CLA protects against DSS-induced colitis in a process involving induction of PPARγ and TFF3.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 98%

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Dietary Conjugated Linoleic Acid Activates PPARγ and the Intestinal Trefoil Factor in SW480 Cells and Mice with Dextran Sulfate Sodium-Induced Colitis3

Borniquel

Jädert

Lundberg

2012

The Journal of Nutrition

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“…However, PPARγ agonists have been reported to foster ulcer healing [20] and protect against gastric ischemiareperfusion damage [19]. Possibly, the stimulating effect on gastric acid secretion is overridden by the simultaneous stimulating effect on trefoil factor expression [17], which are known to exert protective effects [18].…”

Section: Discussionmentioning

confidence: 99%

Pioglitazone Induced Gastric Acid Secretion

Rotte

Mack²,

Bhandaru³

et al. 2009

Cell Physiol Biochem

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PPARγ agonists, such as pioglitazone, are widely used in the treatment of diabetes and several further disorders. They enhance transcription of the serum and glucocorticoid inducible kinase SGK1, which could in turn enhance gastric acid secretion by stimulating KCNQ1 K⁺ channels. The present study explored whether pioglitazone upregulates SGK1 protein expression in gastric glands and thus modifies gastric acid secretion. Food containing the PPARγ agonist pioglitazone (approximately 25mg/kg bw/day) was administered to gene-targeted mice lacking SGK1 (sgk1^-/-, n=11) and their wild-type littermates (sgk1^+/+, n=11). Western blotting was employed to analyze SGK1 expression, BCECF-fluorescence to determine acid secretion in isolated gastric glands and immunohistochemistry to elucidate KCNQ1 and H⁺/K⁺-ATPase protein abundance in the parietal cell membrane. Pioglitazone significantly increased SGK1 expression. Cytosolic pH and cellular buffer capacity were not significantly different between sgk1^+/+and sgk1^-/- mice and not significantly modified in either genotype by pioglitazone. Without pioglitazone treatment, Na⁺-independent pH-recovery following an ammonium pulse (ΔpH/min) reflecting H⁺/K⁺-ATPase activity was again similar in sgk1^+/+and sgk1^-/- mice. Pioglitazone significantly increased ΔpH/min (≈3 fold) in sgk1^+/+ but not in sgk1^-/- mice. H⁺/K⁺-ATPase inhibitor omeprazole (100 μM) abolished ΔpH/min in both genotypes irrespective of pioglitazone treatment. Increase in local K⁺ concentrations to 35 mM (replacing Na⁺/NMDG) significantly increased ΔpH/min and abrogated the differences between genotypes. KCNQ1 and H⁺/K⁺-ATPase protein abundance in the parietal cell membrane was enhanced by pioglitazone treatment in sgk1^+/+but not in sgk1^-/- mice. In conclusion, pioglitazone increases gastric acid secretion, an effect at least partially due to stimulation of SGK1 expression and SGK1-dependent upregulation of KCNQ1.

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“…Gastrin induces TFF2 transcription via two discrete gastrin-responsive promoter elements and via its receptor CCK2R, as well as protein kinase C-, MEK1-and phosphoinositide-3-kinase-dependent, but epidermal growth factor receptor-independent pathways [30 ]. PPAR-g also regulates TFF2 expression in gastric epithelial cells [31 ]. PPAR-g is activated by ligand binding and forms a heterodimer with a retinoid X receptor, which binds to a peroxisome proliferator responsive element, thereby modulating target gene transcription [34].…”

Section: Trefoil Factor Familymentioning

confidence: 97%