SLC4A11 and MFSD3 Gene Expression Changes in Deoxynivalenol Treated IPEC-J2 Cells

Abstract

Deoxynivalenol (DON) caused serious cytotoxicity for animal cells. However, genes involved in regulating DON toxicity and the underlying molecular mechanisms remain largely unknown. This study explored the role of SLC4A11 and MFSD3 in alleviating DON toxicity and analyzed the DNA methylation changes of these two genes. Viability and cell cycle analysis showed that DON exposure decreased the IPEC-J2 viability (P < 0.01), blocked the cell cycle in the G2/M phase (P < 0.01), and increased the rate of apoptosis (P < 0.05). Expression of the SLC4A11 and MFSD3 genes was significantly downregulated upon DON exposure (P < 0.01). Overexpression of SLC4A11 and MFSD3 can enhance the cell viability (P < 0.01). DNA methylation assays indicated that promoter methylation of SLC4A11 (mC-1 and mC-23) and MFSD3 (mC-1 and mC-12) were significantly higher compared with those in the controls and correlated negatively with mRNA expression (P < 0.05). Further analysis showed that mC-1 of SLC4A11 and MFSD3 was located in transcription factor binding sites for NF-1 and Sp1. Our findings revealed the novel biological functions of porcine SLC4A11 and MFSD3 genes in regulating the cytotoxic effects induced by DON, and may contribute to the detection of biomarkers and drug targets for predicting and eliminating the potential toxicity of DON.

Pyroptosis-Mediated Damage Mechanism by Deoxynivalenol in Porcine Small Intestinal Epithelial Cells

“…DON has been especially known to be harmful to pigs; the reason for this is the high bioavailability, glucuronidation metabolism for excretion, lack of detoxification gut microorganisms, and long clearance time [38][39][40]. After the ingestion of DON, it may be rapidly absorbed and accumulate in the small intestinal tract, leading to antifeeding, vomiting, necrosis of the digestive tract, and a decrease in reproductive performance [41,42]. DON exposure causes diverse effects in various body systems, such as the gastrointestinal, neuroendocrine, and reproductive systems, intestinal toxicity, and results in growth impairment and immune dysfunction [36,43].…”

Histone Methyltransferase MLL1 Mediates Oxidative Stress and Apoptosis upon Deoxynivalenol Exposure in the Intestinal Porcine Epithelial Cells

“…There are several different groups including si- MLL1 -NC + DON, si- MLL1 + DON, si- TNFRSF1A -NC and si- TNFRSF1A . After treatments, the samples were performed as described previously [ 20 ]. Cell apoptosis and cell cycle were detected using flow cytometry (Beckman Coulter, Brea, CA, USA), and then analyzed by CytExpert 2.3 and FlowJo 7.6.…”

DNA Methylation of Pig FUT3 Promoter Alters mRNA Expression to Regulate E. coli F18 Susceptibility

“…It has been reported that DNA methylation plays a crucial role in maintaining cell function, regulating individual development and disease [2][3][4]. DNA methylation is considered to be a significant research hotspot in the current field of pig genetics and breeding, relevant studies mainly focus on tissue-specific expression [5,6], cell apoptosis [7], variety differences [8], growth and development [9][10][11], immune response [12,13]. However, DNA methylation has been rarely reported in expression regulation of pig resistance to pathogenic microorganism infection.…”