Abstract
Ochratoxin A (OTA) is a widespread environmental pollutant that is a threat to humans and livestock and remains a global concern to public health. It has negative effects on both humans and animals that are in a continuously exposed environment. The compromised intestinal barrier caused by OTA has aroused widespread concern. This study aimed to investigate the mechanism of OTA-induced tight junction (TJ) protein damage and the relevant components of the intestinal barrier through in vivo whole transcriptome analysis combined with in vitro functional verification. Bioinformatics analysis in OTA-treated Balb/c mice demonstrated that regulated TJ protein related mRNAs were perturbed, and activated the WNT/Ca2+ signaling pathway possibly regulated by key lncRNAs and miRNAs. Competing endogenous RNA (ceRNA) network analysis revealed that lncRNA Zeb1 regulated FZD4 binding with WNT5a to release Ca2+ by targeting miR-1258-x and reduced the expression of TJ proteins, thus damaging the function of the intestinal barrier. An in vitro experiment with Caco-2 cells verified that an increase in Ca2+ level was involved in OTA-induced decreases in the expression of TJ proteins. Taken together, these results will help to identify targets in the intestinal barrier that are compromised by OTA, and will provide the basis for preventing the associated hazard and risk.