AUTHOR=Xu Yafei , Chen Xiaolei , Yu Luchen , Wang Yi , Wang Haifei , Wu Zhengchang , Wu Shenglong , Bao Wenbin 

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

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.697883

DOI=10.3389/fgene.2021.697883

ISSN=1664-8021

ABSTRACT=<p>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 <italic>SLC4A11</italic> and <italic>MFSD3</italic> 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 (<italic>P</italic> &lt; 0.01), blocked the cell cycle in the G2/M phase (<italic>P</italic> &lt; 0.01), and increased the rate of apoptosis (<italic>P</italic> &lt; 0.05). Expression of the <italic>SLC4A11</italic> and <italic>MFSD3</italic> genes was significantly downregulated upon DON exposure (<italic>P</italic> &lt; 0.01). Overexpression of <italic>SLC4A11</italic> and <italic>MFSD3</italic> can enhance the cell viability (<italic>P</italic> &lt; 0.01). DNA methylation assays indicated that promoter methylation of <italic>SLC4A11</italic> (mC-1 and mC-23) and <italic>MFSD3</italic> (mC-1 and mC-12) were significantly higher compared with those in the controls and correlated negatively with mRNA expression (<italic>P</italic> &lt; 0.05). Further analysis showed that mC-1 of <italic>SLC4A11</italic> and <italic>MFSD3</italic> was located in transcription factor binding sites for NF-1 and Sp1. Our findings revealed the novel biological functions of porcine <italic>SLC4A11</italic> and <italic>MFSD3</italic> 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.</p>