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日粮 DON 暴露后猪肝脏、空肠和血清中的 microRNA 表达谱分析揭示候选毒性生物标志物。

MicroRNA Expression Profiling in Porcine Liver, Jejunum and Serum upon Dietary DON Exposure Reveals Candidate Toxicity Biomarkers.

机构信息

BIOMIN Research Center, BIOMIN Holding GmbH, Technopark 1, 3430 Tulln, Austria.

University Clinic for Swine, Department for Farm Animals and Veterinary Public Health, University of Veterinary Medicine Vienna, Veterinaerplatz 1, 1210 Vienna, Austria.

出版信息

Int J Mol Sci. 2021 Nov 7;22(21):12043. doi: 10.3390/ijms222112043.

DOI:10.3390/ijms222112043
PMID:34769473
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8585098/
Abstract

Deoxynivalenol (DON), a frequent mycotoxin worldwide, impairs human and animal health. The response of microRNAs, small non-coding RNAs, to DON has been scarcely investigated, but holds remarkable potential for biomarker applications. Hence, we aimed to investigate DON-induced changes in the microRNA expression in porcine liver, jejunum and serum by combining targeted and untargeted analyses. Piglets received uncontaminated feed or feed containing 900 µg/kg and 2500 µg/kg DON for four weeks, followed by a wash-out period. In tissue, only slight changes in microRNA expression were detected, with ssc-miR-10b being downregulated in liver of DON-exposed piglets. In serum, several microRNAs were differentially expressed upon DON exposure, four of which were validated by qPCR (ssc-miR-16, ssc-miR-128, ssc-miR-451, ssc-miR-205). The serum microRNA response to DON increased over time and declined after removal of contaminated diets. Receiver operating curve analyses for individual microRNAs were significant, and a combination of the four microRNAs increased the predictive capacity for DON exposure. Predicted microRNA target genes showed enrichment of several pathways including PIK3-AKT, Wnt/β-catenin, and adherens junctions. This study gives, for the first time, a comprehensive view of the porcine microRNA response to DON, providing a basis for future research on microRNAs as biomarkers for mycotoxins.

摘要

脱氧雪腐镰刀菌烯醇(DON)是一种在全球范围内普遍存在的真菌毒素,会损害人类和动物的健康。miRNA(微小 RNA)是一类小的非编码 RNA,它们对 DON 的反应尚未得到充分研究,但在生物标志物应用方面具有很大的潜力。因此,我们旨在通过结合靶向和非靶向分析,研究 DON 诱导的猪肝脏、空肠和血清中 microRNA 表达的变化。仔猪接受未污染的饲料或含有 900µg/kg 和 2500µg/kg DON 的饲料喂养四周,随后进行洗脱期。在组织中,仅检测到 microRNA 表达的轻微变化,DON 暴露的仔猪肝脏中 ssc-miR-10b 下调。在血清中,暴露于 DON 后有几个 microRNAs 表达差异,其中 4 个通过 qPCR 验证(ssc-miR-16、ssc-miR-128、ssc-miR-451、ssc-miR-205)。血清 microRNA 对 DON 的反应随时间增加,并在去除污染饮食后下降。单个 microRNA 的接收者操作特征曲线分析具有统计学意义,并且四种 microRNA 的组合增加了 DON 暴露的预测能力。预测的 microRNA 靶基因富集了几个途径,包括 PI3K-AKT、Wnt/β-catenin 和黏着连接。本研究首次全面观察了猪对 DON 的 microRNA 反应,为未来研究 microRNA 作为真菌毒素生物标志物提供了基础。

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