Osmotic changes and ethanol modify TFF gene expression in gastrointestinal cell lines

Abstract

The gastrointestinal tract is exposed to environmental insult as a result of food intake or in pathological conditions such as diarrhoea, and is therefore protected by the mucus layer. As part of it, trefoil peptides (TFFs) are able to modify the viscoelastic properties of the mucus, protect against experimental ulceration, and promote repair of the epithelia. We investigated, using transient reporter gene assays and RT-PCR in the gastric carcinoma cell line MKN45 and colon carcinoma cell lines LS174T and HT29, whether ethanol and osmotic changes can modify transcriptional activity of TFFs. In a mild hypotonic environment (200 mosmol/l) all three TFF genes were upregulated by at least a factor of 2. In hypertonic medium (400 mosmol/l), TFF1 and TFF3 were down-regulated, whereas TFF2 was up-regulated by elevated concentrations of sodium or chloride in MKN45. Raising the osmolality by ethanol resulted in an up-regulation of TFF3 in both colon cell lines but not in the gastric cell line. We conclude that alteration in TFF gene expression is a response of gut epithelia to deal with osmotic forces and ethanol.z 1998 Federation of European Biochemical Societies.

The intestinal factor Tff3 and a miRNA network regulate murine caloric metabolism

“…All three Tff genes were shown to carry various regulatory elements within their promoters and to be regulated by different factors including nutritional components. 36,37 In line with newer observations demonstrating overall gene regulation via miRNA we investigated whether dietary responses and caloric intake mediated by trefoil factors were connected with the miRNA regulatory network. When comparing the miRNA transcriptome in Tff3 KO and wild-type mice a set of 21 significantly deregulated miRNAs was identified.…”

Trefoil factor family 1, MUC5AC and human leucocyte antigen-DR expression by conjunctival cells in patients with glaucoma treated with chronic drugs: could these markers predict the success of glaucoma surgery?

“…Furthermore, TFF gene expression in cells is increased by hypotonicity and an increase in TFF1 secretion can depend on osmotic phenomena. 25 Moreover, of the 66 patients in group B, 51 were treated with a prostaglandin, which might have a protective effect. 12 However, our study is limited by the small size of the group without preservative (n = 11), which could explain the absence of TFF1 and HLA-DR expression and the difference with the preserved-drop group.…”

Tumour necrosis factor and nuclear factor B inhibit transcription of human TFF3 encoding a gastrointestinal healing peptide

“…In gastric and intestinal cell lines, we found that osmotic forces, ethanol, as well as acute phase gene regulators HNF-3 and GATA-6 induced upregulation of TFF genes. [57][58][59] Recently it was reported that duodenal TFF3 expression was low in association with chronic inflammation and villus atrophy in coeliac disease patients, and that recovery following removal of gluten from the diet was accompanied by recovery in TFF3 expression. 60 In humans, upregulation of trefoil genes TFF1 and TFF2 but not TFF3 was observed in IBD.…”