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整合长链非编码 RNA 转录组学、蛋白质组学和代谢组学,以鉴定脱氧雪腐镰刀菌烯醇处理的 IPEC-J2 细胞中的早期细胞反应变化。

Integrated lncRNA transcriptomics, proteomics, and metabolomics to identify early cellular response variation in deoxynivalenol-treated IPEC-J2 cells.

机构信息

Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, China; University of Chinese Academy of Sciences, Beijing, 100008, China.

College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410128, China.

出版信息

Food Chem Toxicol. 2023 Jul;177:113863. doi: 10.1016/j.fct.2023.113863. Epub 2023 May 29.

DOI:10.1016/j.fct.2023.113863
PMID:37257635
Abstract

Mycotoxins, especially deoxynivalenol (DON), are common contaminants of food and feed, which also has serious threaten to human health and livestock production. Moreover, DON severely impair intestinal epithelial barrier function. Therefore, it is necessary to investigate the mechanism of intestinal epithelial cell injury induced by DON. Here, intestinal porcine enterocyte cell (IPEC-J2) was incubated with 200 ng/ml or 2000 ng/ml DON for 6 h, then lncRNA sequencing, metabolomics and proteomics were applied. Combined with long coding transcriptomics, and proteomics, 200 ng/ml DON treatment (LDON group) significantly upregulated ribosome biogenesis in eukaryotes, spliceosome, and ubiquitin mediated proteolysis, RNA transport, and downregulated metabolic pathways in IPEC-J2, 2000 ng/ml of DON treatment (HDON group) significantly upregulated ribosome biogenesis in eukaryotes, and spliceosome, and downregulated base excision repair, cell cycle, DNA replication, homologous recombination, and mismatch repair in IPEC-J2. Combined with long coding transcriptomics, and proteomics, as compared with LDON group, HDON group significantly upregulated adherens junction, hippo signaling pathway, and pathways in cancer, and downregulated DNA replication pathways in IPEC-J2. In metabolomics, LDON group and HDON group was mainly downregulated biosynthesis of unsaturated fatty acids, and fatty acid metabolism. These results provide a new insight to prevent and treat DON induced intestinal epithelial cell injury.

摘要

真菌毒素,尤其是脱氧雪腐镰刀菌烯醇(DON),是食品和饲料中常见的污染物,也对人类健康和畜牧业生产构成严重威胁。此外,DON 严重损害肠道上皮屏障功能。因此,有必要研究 DON 诱导的肠道上皮细胞损伤的机制。本研究采用 200ng/ml 或 2000ng/ml DON 处理猪肠上皮细胞(IPEC-J2)6h,进行 lncRNA 测序、代谢组学和蛋白质组学分析。结合长编码转录组学和蛋白质组学分析,200ng/ml DON 处理(LDON 组)显著上调了 IPEC-J2 中的真核生物核糖体生物发生、剪接体和泛素介导的蛋白水解、RNA 转运,下调了代谢途径;2000ng/ml DON 处理(HDON 组)显著上调了真核生物核糖体生物发生和剪接体,下调了碱基切除修复、细胞周期、DNA 复制、同源重组和错配修复。结合长编码转录组学和蛋白质组学分析,与 LDON 组相比,HDON 组显著上调了 IPEC-J2 中的黏着连接、 Hippo 信号通路和癌症通路,下调了 DNA 复制途径。在代谢组学方面,LDON 组和 HDON 组主要下调了不饱和脂肪酸的生物合成和脂肪酸代谢。这些结果为预防和治疗 DON 诱导的肠道上皮细胞损伤提供了新的思路。

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