Li Bingjue, Xiang Wenyu, Qin Jing, Xu Qiannan, Feng Shi, Wang Yucheng, Chen Jianghua, Jiang Hong
Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Key Laboratory of Nephropathy, Hangzhou, China.
Ann Transl Med. 2021 Apr;9(8):653. doi: 10.21037/atm-20-6632.
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.
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.
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.
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.
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。研究人员已证实长链非编码核糖核酸（lncRNA）在肾脏中的调节功能。然而，很少有研究探讨产前暴露于CPF或lncRNA对肾脏发育的影响。
对产前暴露于CPF的小鼠和二甲基亚砜（DMSO）对照小鼠在胚胎第12.5天、第14.5天、第16.5天和第18.5天获取的胚胎肾脏进行高通量核糖核酸（RNA）测序。应用加权基因共表达网络分析（WGCNA）和功能富集分析构建lncRNA-信使核糖核酸（mRNA）网络并筛选靶向基因。这些策略用于选择与小鼠肾脏发育中产前CPF暴露相关的模块和基因。
基因本体（GO）分析显示，与产前CPF暴露相关的枢纽mRNA主要参与细胞外基质和胶原蛋白降解。Prss1、Prss2和Prss3是上调最显著的mRNA，且均与lncRNAs Gm28760、Gm28139和Gm26717有强连接。此外，我们分析了产前CPF暴露后不同发育阶段肾脏的lncRNA-mRNA网络。结果表明，肾脏发育在胚胎第12.5天受阻，导致在胚胎第18.5天出现异位近端小管形成。
总之，RNA测序和加权基因共表达网络分析表明，产前CPF暴露小鼠模型的肾脏发育中发生了分子表型变化。
