在庆大霉素诱导的急性肾损伤犬模型中筛选尿微小RNA的差异表达谱

Bo Sun, Liang Chen, Z. Qu, Yanwei Yang, Y. Miao, Rui-li Wang, Xiao-bing Zhou, Bo Li
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摘要

微小RNA(miRNA)由于其在生物流体中的稳定和可检测特性,是用于不同病理模型的有前途的生物标志物。在这里,我们收集了5只比格犬在庆大霉素引起的急性肾损伤(AKI)第3天、第6天和第12天的尿液样本。通过高通量测序测量miRNA水平,然后对结果进行差异研究。进行基因本体论(GO)和KEGG通路分析,以分析与差异表达的miRNA(DE-miRNA)相对应的潜在靶基因。用STRING和Cytoscape分析枢纽基因和DE miRNA之间的关系。庆大霉素治疗后3、6和12天,我们鉴定了234个DE miRNA(p<0.05)。通过重叠的TargetScan和miRanda结果预测了DE miRNA的前10个上调和下调候选靶基因。GO和KEGG对DE miRNA的分析表明,DE miRNA靶基因主要参与肾损伤相关通路,如胰岛素信号通路、催产素信号通路和刺猬信号通路。miRNA中枢基因网络表明,miR-452、miR-106a和106b参与调节数量最多的中枢基因。我们通过庆大霉素引起的急性肾损伤建立的犬模型来评估miRNA特征。我们的研究结果为评估miRNA作为肾毒性生物标志物提供了宝贵的资源。
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Screening Differential Expression Profiles of Urinary microRNAs in a Gentamycin-Induced Acute Kidney Injury Canine Model
microRNAs (miRNAs) are promising biomarkers for different pathological models because of their stable and detectable characters in biofluids. Here, we collected urine samples from 5 beagle dogs on the 3th, 6th, and 12th day in an acute kidney injury (AKI) caused by gentamycin. miRNA levels were measured with high-throughput sequencing and the results were then differentially investigated. Gene Ontology (GO) and KEGG pathway analysis were performed to analyze potential target genes corresponding to the differentially expressed miRNAs (DE-miRNAs). Relationships between hub genes and DE-miRNAs were analyzed with STRING and Cytoscape. We identified 234 DE-miRNAs 3, 6, and 12 days after gentamycin treatment (p < 0.05). Top 10 up- and down-regulated candidate target genes of DE-miRNAs were predicted by overlapping TargetScan and miRanda results). GO and KEGG analyses for DE-miRNAs demonstrated that the DE-miRNAs target genes are mainly involved in kidney injury-related pathways, such as the insulin signaling pathway, oxytocin signaling pathway, and hedgehog signaling pathway. The network of miRNA-hub genes suggests that miR-452, miR-106a, and 106b participate in regulating the largest number of hub genes. We evaluated the miRNA signature via a canine model built by gentamycin-caused acute kidney injury. Our results represent a valuable resource for evaluating miRNAs as biomarkers of renal toxicity.
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