Proteome changes induced by a short, non-cytotoxic exposure to the mycoestrogen zearalenone in the pig intestine
Résumé
Intestinal epithelial homeostasis is regulated by a complex network of signaling pathways. Among them is es-trogen signaling, important for the proliferation and differentiation of epithelial cells, immune signaling andmetabolism. The mycotoxin zearalenone (ZEN) is an estrogen disruptor naturally found in food and feed. Theexposure of the intestine to ZEN has toxic effects including alteration of the immune status and is possiblyimplicated in carcinogenesis, but the molecular mechanisms linked with these effects are not clear. Our objectivewas to explore the proteome changes induced by a short, non-cytotoxic exposure to ZEN in the intestine using pigjejunal explants. Our results indicated that ZEN promotes little proteome changes, but significantly related withan induction of ERαsignaling and a consequent disruption of highly interrelated signaling cascades, such as NF-κB, ERK1/2, CDX2 and HIF1α. The toxicity of ZEN leads also to an altered immune status characterized by theactivation of the chemokine CXCR4/SDF-1 axis and an accumulation of MHC-I proteins. Our results connect theestrogen disrupting activity of ZEN with its intestinal toxic effect, associating the exposure to ZEN with cell-signaling disorders similar to those involved in the onset and progression of diseases such as cancer and chronicinflammatory disorders.Significance:The proteomics results presented in our study indicate that the endocrine disruptor activity of ZENis able to regulate a cascade of highly inter-connected signaling events essential for the small intestinal crypt-villus cycle and immune status. These molecular mechanisms are also implicated in the onset and progress ofintestinal immune disorders and cancer indicating that exposure to ZEN could play an important role in in-testinal pathogenesis
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