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首页> 外文期刊>Archives of Toxicology >Deoxynivalenol inhibits the expression of trefoil factors (TFF) by intestinal human and porcine goblet cells
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Deoxynivalenol inhibits the expression of trefoil factors (TFF) by intestinal human and porcine goblet cells

机译：脱氧性苯酚抑制肠道人和猪脚卵细胞的三叶子因子（TFF）的表达

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摘要

Trefoil factors (TFFs) are bioactive peptides expressed by several epithelia, including the intestine, where they regulate key functions such as tissue regeneration, barrier function and inflammation. Although food-associated mycotoxins, including deoxynivalenol (DON), are known to impact many intestinal functions, modulation of TFFs during mycotoxicosis has never been investigated. Here, we analyzed the effect of DON on TFFs expression using both human goblet cells (HT29-16E cells) and porcine intestinal explants. Results showed that very low doses of DON (nanomolar range) inhibit the secretion of TFFs by human goblet cells (IC50 of 361, 387 and 243nM for TFF1, 2 and 3, respectively) and prevent wound healing. RT-qPCR analysis demonstrated that the inhibitory effect of DON is related to a suppression of TFFs mRNA expression. Experiments conducted on porcine intestinal explants confirmed the results obtained on cells. Finally, the use of specific inhibitors of signal pathways demonstrated that DON-mediated suppression of TFFs expression mainly involved Protein Kinase R and the MAP kinases (MAPK) p38 and ERK1/2. Taken together, our results show for the first time that at very low doses, DON suppresses the expression and production of intestinal TFFs and alters wound healing. Given the critical role of TFFs in tissue repair, our results suggest that DON-mediated suppression of TFFs contributes to the alterations of intestinal integrity the caused by this toxin.
机译：Trefoil因子（TFF）是由几种上皮表达的生物活性肽，包括肠道，其中它们调节组织再生，屏障功能和炎症等关键功能。虽然众所周知，食物相关的霉菌毒素（包括脱氧苯酚（Don）），但是患有许多肠功能，因此从未调查过霉菌毒病期间TFF的调节。在这里，我们分析了DON对TFFS表达的效果，使用人脚卵细胞（HT29-16E细胞）和猪肠道外植体。结果表明，非常低剂量的唐（纳米摩尔范围）抑制人脚杯细胞（分别为TFF1,2和3的361,387和243nm的IC 50的TFF分泌并防止伤口愈合。 RT-QPCR分析证明DON的抑制作用与TFFS mRNA表达的抑制有关。对猪肠外分布植体进行的实验证实了在细胞上获得的结果。最后，使用信号途径的特定抑制剂证明了TFFS表达的抑制主要涉及蛋白激酶R和地图激酶（MAPK）P38和ERK1 / 2。我们的结果展示了第一次在非常低的剂量上显示，唐抑制了肠TFF的表达和生产，并改变了伤口愈合。鉴于TFFS在组织修复中的关键作用，我们的结果表明，唐介导的TFF抑制有助于这种毒素引起的肠道完整性的改变。

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