Co-expression network of long non-coding RNA and mRNA reveals molecular phenotype changes in kidney development of prenatal chlorpyrifos exposure in a mouse model.

Co-expression network of long non-coding RNA and mRNA reveals molecular phenotype changes in kidney development of prenatal chlorpyrifos exposure in a mouse model.
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长非编码RNA和mRNA的共表达网络揭示了小鼠模型中产前毒死蜱暴露对肾脏发育的分子表型变化

DOI:
10.21037/atm-20-6632
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发表时间:
2021-04
影响因子:
--
通讯作者:
Jiang H
Jiang H
中科院分区:
医学4区
文献类型:
--
作者:
Li B;Xiang W;Qin J;Xu Q;Feng S;Wang Y;Chen J;Jiang H

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背景毒死蜱(CPF)是全球使用最广泛的有机磷农药之一,可在肾脏中蓄积。研究人员已经证实了肾脏中长非编码核糖核酸(LncRNA)的调节功能。然而,很少有研究考察产前CPF暴露或lncRNA对肾脏发育的影响。方法应用高通量核糖核酸(RNA)测序技术,对孕期接触CPF的小鼠和二甲基亚砜(DMSO)对照组小鼠胚胎肾脏进行高通量核糖核酸测序。应用加权基因共表达网络分析(WGCNA)和功能富集度分析构建LncRNA-信使核糖核酸(MRNAs)网络,筛选靶基因。这些策略被用来选择与出生前CPF暴露在小鼠肾脏发育中相关的模块和基因。结果基因本体论(GO)分析表明,与产前CPF暴露相关的Hub mRNAs主要参与细胞外基质和胶原降解。Prss 1、Prss 2和Prss 3是最显著上调的mRNAs,并且都与lncRNAs Gm28760、Gm28139和Gm26717有很强的联系。此外,我们还分析了出生前暴露于CPF后不同发育阶段肾脏中的lncRNA-mRNA网络。结果表明,胚胎12.5天肾脏发育受阻,导致胚胎18.5天近端小管异位形成。结论综上所述,RNA测序和加权基因共表达网络分析表明,在出生前CPF暴露的小鼠模型中,肾脏发育过程中发生了分子表型变化。
Background Chlorpyrifos (CPF) is one of the most widely used organophosphorus pesticides globally and can accumulate in the kidney. Researchers have confirmed the regulatory functions of long non-coding ribonucleic acid (lncRNA) in the kidney. However, very few studies have examined the effects of prenatal CPF exposure or lncRNA on kidney development. Methods High-throughput ribonucleic acid (RNA) sequencing was performed on embryonic kidneys obtained at E12.5, E14.5, E16.5, and E18.5 of prenatal CPF-exposed mice and the dimethyl sulfoxide (DMSO) control mice. A weighted gene co-expression network analysis (WGCNA) and a functional enrichment analysis were applied to construct a lncRNA-messenger ribonucleic acid (mRNA) network and screen targeted genes. These strategies were used to select the modules and genes correlated with prenatal CPF exposure in mouse kidney development. Results A gene ontology (GO) analysis revealed that the hub mRNAs linked to prenatal CPF exposure were mainly involved in the extracellular matrix and collagen degradation. Prss1, Prss2, and Prss3 were the most significantly upregulated mRNAs, and all had strong connections to lncRNAs Gm28760, Gm28139, and Gm26717. Additionally, we analyzed the lncRNA-mRNA network at different developmental kidney stages after prenatal CPF exposure. The results showed that kidney development was blocked at E12.5, which led to ectopic proximal tubule formation at E18.5. Conclusions In summary, the RNA-sequencing and weighted gene co-expression network analyses showed that molecular phenotype changes occur in kidney development in a prenatal CPF exposure mouse model.
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