Deoxynivalenol triggers porcine intestinal tight junction disorder: Insights from mitochondrial dynamics and mitophagy

Abstract

Deoxynivalenol (DON) is universally detected trichothecene in most cereal commodities, which is considered as a major hazardous material for human and animal health. Intestine is the most vulnerable organ with higher concentration of DON than other organs, owing to the first defense barrier function to exogenous substances. However, the underling mechanisms about DON-induced intestinal toxicity remain poorly understood. Here, DON poisoning models of IPEC-J2 cells was established to explore adverse effect and the potential mechanism of DON-induced enterotoxicity. Results showed that DON exposure destroyed IPEC-J2 cells morphology. Results showed that DON exposure destroyed IPEC-J2 cells morphology. Intestinal epithelial barrier injury was caused by DON with increasing LDH release, decreasing cell viability as well decreasing tight junction protein expressions (Occludin, N-Cad, ZO-1, Claudin-1 and Claudin-3). Moreover, DON caused mitochondrial dysfunction by opening mitochondrial permeability transition pore and eliminating mitochondrial membrane potential. DON exposure upregulated protein and mRNA expression of mitochondrial fission factors (Drp1, Fis1, MIEF1 and MFF) and mitophagy factors (PINK1, Parkin and LC3), downregulated mitochondrial fusion factors (Mfn1, Mfn2, except OPA1), resulting in mitochondrial dynamics imbalance and mitophagy. Overall, these findings suggested that DON induced tight junction dysfunction in IPEC-J2 cells was related to mitochondrial dynamics-mediated mitophagy.