Abstract：
Diquat (DQ) is a commonly used bipyridine herbicide known for its toxic properties and adverse effects on individuals. However, the mechanism underlying DQ-induced damage remain elusive. Our research aimed to uncover the regulatory network involved in DQ-induced damage. We analyzed publicly accessible gene expression patterns and performed research using a DQ-induced damage animal model. The GSE153959 dataset from the Gene Expression Omnibus collection and the animal model of DQ-induced kidney injury were used to identify differentially expressed genes (DEGs). Pathways including the regulation of DNA-templated transcription in response to stress, RNA polymerase II transcription regulator complex and transcription coregulatory activity were shown to be enriched in 21 DEGs. We used least absolute shrinkage and selection operator (LASSO) regression analysis to find possible diagnostic biomarkers for DQ-induced damage. Then, we used an HK-2 cell model to confirm these results. Additionally, we confirmed that 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) was the major gene associated with DQ-induced damage using multi-omics screening. The sample validation strongly suggested that HMGCS2 has promise as a diagnostic marker and may provide new targets for therapy in the context of DQ-induced damage.
摘要：
Diquat（DQ）是一种常用的联吡啶除草剂，以其毒性和对个体的不利影响而闻名。然而,DQ诱导损伤的潜在机制仍然难以捉摸。我们的研究旨在揭示DQ引起的损害所涉及的监管网络。我们分析了可公开获得的基因表达模式，并使用DQ诱导的损伤动物模型进行了研究。来自基因表达综合收集的GSE153959数据集和DQ诱导的肾损伤的动物模型用于鉴定差异表达的基因(DEGs)。途径包括调节DNA模板化转录以应对压力，RNA聚合酶II转录调节复合物和转录共调节活性显示在21个DEGs中富集。我们使用最小绝对收缩和选择算子（LASSO）回归分析来寻找DQ诱导损伤的可能的诊断生物标志物。然后，我们使用HK-2细胞模型来证实这些结果.此外,我们通过多组学筛选证实,3-羟基-3-甲基戊二酰辅酶A合酶2(HMGCS2)是与DQ诱导的损伤相关的主要基因.样品验证强烈表明HMGCS2有望作为诊断标记物，并可能为DQ诱导的损伤提供新的治疗靶标。
