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

Abstract

BackgroundChlorpyrifos (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.MethodsHigh-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.ResultsA 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.ConclusionsIn 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.