The transcriptome of nitrofen-induced pulmonary hypoplasia in the rat model of congenital diaphragmatic hernia
The transcriptome of nitrofen-induced pulmonary hypoplasia in the rat model of congenital diaphragmatic hernia
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DOI：
10.1038/pr.2015.277
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发表时间：
2016-05-01
影响因子：
3.6
通讯作者：
Keijzer, Richard
中科院分区：
文献类型：
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作者：
Mahood, Thomas H.;Johar, Dina R.;Keijzer, Richard
背景：目前尚不清楚除草剂硝苯醚是如何引起大鼠肺发育不良和先天性横隔疝的。我们的目的是比较胚胎发育第13天的大鼠胚胎中硝苯醚诱导的发育不良肺和对照肺的差异表达转录组。方法：利用下一代测序技术，我们鉴定了microRNA(MiRNA)和mRNA基因的表达谱。当数据集被RT-qPCR和Digital-PCR验证后，我们对去调控的矽肺中miRNAs进行了基因本体、miRNA靶标分析和同源miRNA序列匹配。结果：我们的研究发现了186个已知的mRNAs和100个miRNAs在硝苯醚诱导的发育不良肺中差异表达。鉴定了64个与已知人类miRNAs同源的大鼠miRNAs。这些基因的一个子集可能促进大鼠和/或人类的肺发育不良，我们讨论了它们之间的联系。与硝苯醚诱导的肺发育不良相关的miRNA途径包括PI3K、转化生长因子-β和细胞周期蛋白激酶。结论：硝苯芬诱导的肺发育不良存在转录组异常，可能导致发育障碍。
BACKGROUND: We currently do not know how the herbicide nitrofen induces lung hypoplasia and congenital diaphragmatic hernia in rats. Our aim was to compare the differentially expressed transcriptome of nitrofen-induced hypoplastic lungs to control lungs in embryonic day 13 rat embryos before the development of embryonic diaphragmatic defects.METHODS: Using next-generation sequencing technology, we identified the expression profile of microRNA (miRNA) and mRNA genes. Once the dataset was validated by both RT-qPCR and digital-PCR, we conducted gene ontology, miRNA target analysis, and orthologous miRNA sequence matching for the deregulated miRNAs in silico.RESULTS: Our study identified 186 known mRNA and 100 miRNAs which were differentially expressed in nitrofen-induced hypoplastic lungs. Sixty-four rat miRNAs homologous to known human miRNAs were identified. A subset of these genes may promote lung hypoplasia in rat and/or human, and we discuss their associations. Potential miRNA pathways relevant to nitrofen-induced lung hypoplasia include PI3K,TGF-beta, and cell cycle kinases.CONCLUSION: Nitrofen-induced hypoplastic lungs have an abnormal transcriptome that may lead to impaired development.