Schyman Patric, Printz Richard L, Estes Shanea K, Boyd Kelli L, Shiota Masakazu, Wallqvist Anders
DoD Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command, Fort Detrick, MD, United States.
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, United States.
Front Pharmacol. 2018 Nov 6;9:1272. doi: 10.3389/fphar.2018.01272. eCollection 2018.
Ingestion or exposure to chemicals poses a serious health risk. Early detection of cellular changes induced by such events is vital to identify appropriate countermeasures to prevent organ damage. We hypothesize that chemically induced organ injuries are uniquely associated with a set (module) of genes exhibiting significant changes in expression. We have previously identified gene modules specifically associated with organ injuries by analyzing gene expression levels in liver and kidney tissue from rats exposed to diverse chemical insults. Here, we assess and validate our injury-associated gene modules by analyzing gene expression data in liver, kidney, and heart tissues obtained from Sprague-Dawley rats exposed to thioacetamide, a known liver toxicant that promotes fibrosis. The rats were injected intraperitoneally with a low (25 mg/kg) or high (100 mg/kg) dose of thioacetamide for 8 or 24 h, and definite organ injury was diagnosed by histopathology. Injury-associated gene modules indicated organ injury specificity, with the liver being most affected by thioacetamide. The most activated liver gene modules were those associated with inflammatory cell infiltration and fibrosis. Previous studies on thioacetamide toxicity and our histological analyses supported these results, signifying the potential of gene expression data to identify organ injuries.
摄入或接触化学物质会带来严重的健康风险。尽早检测此类事件诱导的细胞变化对于确定预防器官损伤的适当对策至关重要。我们假设化学诱导的器官损伤与一组（模块）表达发生显著变化的基因存在独特关联。我们之前通过分析暴露于多种化学损伤的大鼠肝脏和肾脏组织中的基因表达水平，确定了与器官损伤特异性相关的基因模块。在此，我们通过分析从暴露于硫代乙酰胺（一种已知的促进纤维化的肝脏毒物）的斯普拉格-道利大鼠获得的肝脏、肾脏和心脏组织中的基因表达数据，评估并验证我们的损伤相关基因模块。给大鼠腹腔注射低剂量（25毫克/千克）或高剂量（100毫克/千克）的硫代乙酰胺8或24小时，通过组织病理学诊断明确的器官损伤。损伤相关基因模块显示出器官损伤特异性，肝脏受硫代乙酰胺影响最大。最活跃的肝脏基因模块是那些与炎症细胞浸润和纤维化相关的模块。先前关于硫代乙酰胺毒性的研究以及我们的组织学分析支持了这些结果，表明基因表达数据在识别器官损伤方面的潜力。
