Deoxycholic Acid Modulates Cell-Junction Gene Expression and Increases Intestinal Barrier Dysfunction

• Published in: Molecules (Basel, Switzerland) Vol. 27; no. 3; p. 723
• Main Authors: Zeng, Huawei, Safratowich, Bryan D, Cheng, Wen-Hsing, Larson, Kate J, Briske-Anderson, Mary
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.01.2022; MDPI
• Subjects: Adhesion; Bile; bile acid; Bile acids; Caco-2 Cells; Cell growth; cell junction; Cell junctions; Cell Proliferation; Cholagogues and Choleretics - pharmacology; Colon - drug effects; Colon - metabolism; Colorectal cancer; Deoxycholic acid; Deoxycholic Acid - pharmacology; Dietary intake; Epithelial cells; Epithelium; Extracellular signal-regulated kinase; Gene expression; Gene Expression Regulation - drug effects; Humans; Intercellular Junctions - drug effects; Intercellular Junctions - genetics; Intercellular Junctions - metabolism; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; intestinal permeability; Intestine; Oxidative stress; Permeability; Phenols; Proteins; Tight junctions; cell junction; intestinal permeability; deoxycholic acid; bile acid; gene expression
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27030723

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.