Étude des mécanismes de régulation de la sécrétion et de l'expression des mucines gastrointestinales par la leptine

LYON1-BU.Sciences (692662101) / SudocSudocFranceF

Oleic Acid Uptake Reveals the Rescued Enterocyte Phenotype of Colon Cancer Caco-2 by HT29-MTX Cells in Co-Culture Mode

Gastrointestinal epithelium is the unique route for nutrients and for many pharmaceuticals to enter the body. The present study aimed to analyze precisely whether co-culture of two colon cancer cell lines, mucus-producing cells HT29-MTX and enterocyte-like Caco-2 cells, ameliorate differentiation into an in vitro intestinal barrier model and the signaling pathways involved. Differentiated Caco-2 cells gene datasets were compared first to intestinal or cancer phenotypes and second to signaling pathway gene datasets. Experimental validations were performed in real-time experiments, immunochemistry, and gene expression analyses on Caco-2 versus co-cultures of Caco-2 and HT29-MTX (10%) cells. Partial maintenance of cancer-cell phenotype in differentiated Caco-2 cells was confirmed and fatty acids merged as potential regulators of cancer signaling pathways. HT29-MTX cells induced morphological changes in Caco-2 cells, slightly increased their proliferation rate and profoundly modified gene transcription of phenotype markers, fatty acid receptors, intracellular transporters, and lipid droplet components as well as functional responses to oleic acid. In vitro, enterocyte phenotype was rescued partially by co-culture of cancer cells with goblet cells and completed through oleic acid interaction with signaling pathways dysregulated in cancer cells

Variants of β-casofensin, a bioactive milk peptide, differently modulate the intestinal barrier: In vivo and ex vivo studies in rats

β-Casofensin is a bioactive milk peptide that modulates the intestinal barrier, particularly through itsaction on goblet cells. β-Casofensin corresponds to fragment (f) 94–123 of the bovine β-casein (β-CN) A2variant. Fifteen genetic variants of bovine β-CN (A1–3,B–G, H1–2, I–L) are known, of which the A2, A1, andB forms are the most common. These variants differfrom each other by the substitution of one or moreamino acids, some of which are localized in f94 to 123.The aim of our study was to compare the intestinaleffects of β-casofensin A2 and its 3 main variants: A1,A3, and B. For this purpose, a solution (0.1 µM; 10μL/g of body weight, postnatal d 10–20) containing β-casofensin A2, one of its variants (A1, A3, or B), ordrinking water (control; CT) was administered to rat pups orally. After euthanasia (postnatal d 20), intestinalsegments were collected for biochemical and histochemical analysis and also used to determine paracellularpermeability to fluorescein isothiocyanate-labeled 4-kDa dextran in an Ussing chamber. We also studiedthe direct effects of β-casofensin A2 and its A1 variant on the paracellular permeability of jejunum segmentsof adult rats. β-Casofensin A2 and its B variant significantly increased the population of goblet cells comparedwith the CT, A1, and A3 groups. The mucin 2 mRNA level was significantly higher in the β-casofensinA2 group than in the CT, A3, and B groups. Our results also revealed that the protein expression of zonulaoccludens-1 and occludin was reduced in the jejunum of rats in the A1, A3, and B groups compared with theCT group. However, the A1 variant was the only peptide to decrease jejunal permeability compared with theCT group. This variant, tested directly in the apical compartment of an Ussing chamber at a concentrationof 0.1 nM, also reduced jejunal permeability. In conclusion, the substitution of a single amino acid altersthe effect of β-CN sequence f94 to 123 on goblet cells and on intestinal permeability. A genetic polymorphismof β-CN can affect the biological activity of peptides derived from this protein. These data should be takeninto account in the production of bioactive foods. Key words: bioactive milk peptide, β-casein, β-CN(94-123), intestinal protectio

Peptides augmentant la secrétion et/ou l'expression d'au moins une mucine gastrointestinale et/ou induisant l'augmentation de la population de cellules à mucus ou de cellules de paneth.

The invention relates to a polypeptide including or consisting of SEQ ID NO: 1, or a sequence at least 80% identical to SEQ ID NO: 1, or a sequence of at least 4 consecutive amino acids included in SEQ ID NO: 1, wherein said polypeptide has at least one effect selected from: inducing the expression and/or the secretion of at least one gastrointestinal mucin; and inducing the expression and/or the secretion of at least one intestinal defense molecule expressed by Paneth cells; and inducing an increase in the population of mucus cells and/or in the population of Paneth cells, with the proviso that the polypeptide does not include the SEQ ID NO: 2 sequence

Dietary emulsifiers from milk and soybean differently impact adiposity and inflammation in association with modulation of colonic goblet cells in high-fat fed mice

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