Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China.
Joint International Research Laboratory of Agriculture & Agri-Product Safety, Yangzhou University, Yangzhou 225009, China.
Int J Mol Sci. 2022 Oct 22;23(21):12712. doi: 10.3390/ijms232112712.
Deoxynivalenol (DON) is a type of mycotoxin that threatens human and livestock health. Right open reading frame kinase 2 (RIOK2) is a kinase that has a pivotal function in ribosome maturation and cell cycle progression. This study aims to clarify the role of the gene in DON-induced cytotoxicity regulation in porcine intestinal epithelial cells (IPEC-J2). Cell viability assay and flow cytometry showed that the knockdown of inhibited proliferation and induced apoptosis, cell cycle arrest, and oxidative stress in DON-induced IPEC-J2. Then, transcriptome profiling identified candidate genes and pathways that closely interacted with both DON cytotoxicity regulation and expression. Furthermore, interference promoted the activation of the MAPK signaling pathway by increasing the phosphorylation of ERK and JNK. Additionally, we performed the dual-luciferase reporter and ChIP assays to elucidate that the expression of was influenced by the binding of transcription factor Sp1 with the promoter region. Briefly, the reduced expression of the gene exacerbates the cytotoxic effects induced by DON in IPEC-J2. Our findings provide insights into the control strategies for DON contamination by identifying functional genes and effective molecular markers.
脱氧雪腐镰刀菌烯醇（DON）是一种威胁人类和牲畜健康的真菌毒素。真核起始因子 4E 结合蛋白 1（EIF4EBP1）是一种在核糖体成熟和细胞周期进程中具有关键功能的激酶。本研究旨在阐明该基因在 DON 诱导的猪肠上皮细胞（IPEC-J2）细胞毒性调节中的作用。细胞活力测定和流式细胞术显示， 基因敲低抑制了增殖，并诱导了 DON 诱导的 IPEC-J2 细胞凋亡、细胞周期停滞和氧化应激。然后，转录组谱分析鉴定了与 DON 细胞毒性调节和 表达密切相互作用的候选基因和途径。此外， 干扰通过增加 ERK 和 JNK 的磷酸化来促进 MAPK 信号通路的激活。此外，我们进行了双荧光素酶报告和 ChIP 测定，以阐明转录因子 Sp1 与启动子区域的结合影响 表达。简而言之， 基因表达的减少加剧了 DON 诱导的 IPEC-J2 细胞毒性作用。我们的研究结果为通过鉴定功能基因和有效的分子标记来控制 DON 污染提供了新的思路。
