Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease

Figure 7 Elafibranor on the ethanol-stimulated human intestinal epithelial cells. A: Intracellular mRNA levels of tight junction proteins (TJPs) including zonula occludens-1 (ZO-1), Ocln, and Cldn2 in ethanol (EtOH)-stimulated Caco-2 cells (n = 6); B: Integrity of the epithelial cellular barrier in EtOH-stimulated Caco-2 cells determined as transepithelial electrical resistance (TEER) (n = 6). Cells were incubated with different concentration of EtOH (0, 10, 25, and 50 mmol/L) for 120 minutes (A) and 0, 30, 60, and 120 minutes (B); C: Effect of elafibranor (EFN) on the TJPs mRNA expression in the EtOH-stimulated Caco-2 cells (n = 6); D: Effect of EFN on the TEER in the EtOH-stimulated Caco-2 cells (n = 6). Cells were incubated with EtOH (0 or 50 mmol/L) and EFN (0, 5, 10, 30 μM) for 120 minutes (C) or 0, 30, 60, and 120 minutes (D) following pretreatment with GW7647 (10 μM) or GSK3787 (10 μM) for 15 minutes; E: Effect of EFN on the intracellular caspase 3/7 activity in the EtOH-stimulated Caco-2 cells (n = 6); F: Effect of EFN on mRNA expression of the markers related to autophagy in the EtOH-stimulated Caco-2 cells (n = 6). Cells were incubated with EtOH (0 or 50 mmol/L) and EFN (0 or 30 μM) for 48 hours following pretreatment with a peroxisome proliferator activated receptor (PPAR)α antagonist, GW7647 (10 μM) or a PPARδ antagonist, GSK3787 (10 μM) for 6 hours (E and F). Glyceraldehyde-3-phosphate dehydrogenase was used as an internal control for real-time quantitative polymerase chain reaction (A, C, and F). Quantitative values are indicated as fold changes to the values of EtOH (-)/EFN (0 μM)-treated group (A, C, E, and F). Data are the mean ± SD. ^bP < 0.01 vs ethanol (-)/elafibranor (0 μM)-treated group; ^cP < 0.05 vs ethanol (+)/elafibranor (0 μM)-treated group; ^dP < 0.01 vs ethanol (+)/elafibranor (0 μM)-treated group; ^eP < 0.05 vs ethanol (+)/elafibranor (30 μM)-treated group; ^fP < 0.01 vs ethanol (+)/elafibranor (30 μM)-treated group. EtOH: Ethanol; EFN: Elafibtanor; TEER: Transepithelial electrical resistance; ZO-1: Zonula occludens-1.