Abstract：
Deoxynivalenol (DON) is one of the frequent Fusarium mycotoxins and poses a serious threat to public health worldwide. DON-induced weight loss is tightly connected with its ability to decrease feed intake by influencing gastrointestinal tract (GIT) motility. Our previous reports indicated that DON interfered with intestinal motility by injuring the contractility of enteric smooth muscle cells (SMC). Here, we further explored the potential mechanisms by employing a complementary method of transcriptomics and proteomics using the porcine enteric smooth muscle cell line (PISMC) as an experimental model. The transcriptomic and proteomic data uncover that the expression of numerous extracellular matrix (ECM) proteins and multiple integrin subunits were downregulated in PISMC under DON exposure, suppressing the ECM-integrin receptor interaction and its mediated signaling. Furthermore, DON treatment could depress actin polymerization, as reflected by the upregulated expression of Rho GTPase-activating proteins and cofilin in PISMC. Meanwhile, the expression levels of downstream contractile apparatus genes were significantly inhibited after challenge with DON. Taken together, the current results suggest that DON inhibits enteric SMC contractility by regulating the ECM-integrin-actin polymerization signaling pathway. Our findings provide novel insights into the potential mechanisms behind the DON toxicological effects in the GIT of humans and animals.
摘要：
脱氧雪腐镰刀菌烯醇（DON）是常见的镰刀菌真菌毒素之一，对全球公共卫生构成严重威胁。DON诱导的体重减轻与其通过影响胃肠道（GIT）运动性来减少采食量的能力密切相关。我们以前的报道表明，DON通过损害肠平滑肌细胞（SMC）的收缩性来干扰肠运动。这里,我们以猪肠道平滑肌细胞系(PISMC)为实验模型,采用转录组学和蛋白质组学的互补方法,进一步探索了潜在的机制.转录组和蛋白质组数据揭示了许多细胞外基质（ECM）蛋白和多个整合素亚基的表达在DON暴露下在PISMC中下调，抑制ECM-整联蛋白受体相互作用及其介导的信号传导。此外，DON处理可以抑制肌动蛋白的聚合，如PISMC中RhoGTP酶激活蛋白和cofilin的上调表达所反映的。同时,用DON攻击后，下游收缩器基因的表达水平受到显着抑制。一起来看,目前的结果表明DON通过调节ECM-整合素-肌动蛋白聚合信号通路抑制肠SMC收缩性。我们的发现为人类和动物GIT中DON毒理学效应背后的潜在机制提供了新的见解。
