Deoxycholic Acid Modulates Cell-Junction Gene Expression and Increases Intestinal Barrier Dysfunction
| Autor: | Huawei Zeng, Bryan D. Safratowich, Wen-Hsing Cheng, Kate J. Larson, Mary Briske-Anderson |
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| Rok vydání: | 2021 |
| Předmět: |
Cholagogues and Choleretics
cell junction bile acid deoxycholic acid gene expression intestinal permeability Colon Pharmaceutical Science Organic chemistry Permeability Analytical Chemistry QD241-441 Intercellular Junctions Gene Expression Regulation Chemistry (miscellaneous) Drug Discovery Molecular Medicine Humans Physical and Theoretical Chemistry Caco-2 Cells Intestinal Mucosa Cell Proliferation Deoxycholic Acid |
| Zdroj: | Molecules, Vol 27, Iss 723, p 723 (2022) Molecules; Volume 27; Issue 3; Pages: 723 |
| ISSN: | 1420-3049 |
| Popis: | Diet-related obesity is associated with increased intestinal hyperpermeability. High dietary fat intake causes an increase in colonic bile acids (BAs), particularly deoxycholic acid (DCA). We hypothesize that DCA modulates the gene expression of multiple cell junction pathways and increases intestinal permeability. With a human Caco-2 cell intestinal model, we used cell proliferation, PCR array, biochemical, and immunofluorescent assays to examine the impact of DCA on the integrity of the intestinal barrier and gene expression. The Caco-2 cells were grown in monolayers and challenged with DCA at physiological, sub-mM, concentrations. DCA increased transcellular and paracellular permeability (>20%). Similarly, DCA increased intracellular reactive oxidative species production (>100%) and accompanied a decrease (>40%) in extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathways. Moreover, the mRNA levels of 23 genes related to the epithelial barrier (tight junction, focal adhesion, gap junction, and adherens junction pathways) were decreased (>40%) in (0.25 mM) DCA-treated Caco-2 cells compared to untreated cells. Finally, we demonstrated that DCA decreased (>58%) the protein content of occludin present at the cellular tight junctions and the nucleus of epithelial cells. Collectively, DCA decreases the gene expression of multiple pathways related to cell junctions and increases permeability in a human intestinal barrier model. |
| Databáze: | OpenAIRE |
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