Dynamic metabolic change is indicative of inflammation-induced transformation of hepatic cells
Dynamic metabolic change is indicative of inflammation-induced transformation of hepatic cells
复制标题
动态代谢变化表明炎症诱导的肝细胞转化。
DOI：
10.1016/j.biocel.2015.07.007
复制
发表时间：
2015-09-01
影响因子：
4
通讯作者：
Shi, Song-Lin
中科院分区：
文献类型：
--
作者：
Peng, Bo;Liu, Fan;Shi, Song-Lin
长期的炎症在癌症发展中起着致病作用的观察已经得到了很好的证明。然而，一个渐进的过程，导致从健康到恶性表型尚未被描述。实验诱导的肝细胞癌被认为是研究这一过程的代表性实验室模型之一。肝脏暴露于病毒感染或毒性试剂导致慢性炎症并逐渐转化为肝细胞癌。在这里，我们提出了代谢组学档案的肝细胞在不同阶段的炎症诱导的细胞转化的N-亚硝基二乙胺。利用气相色谱-质谱联用技术，我们定量评估了肝炎和肝硬化转化过程中细胞代谢产物的变化。对差异表达的代谢产物的进一步途径分析表明，肝炎和肝硬化中的糖代谢和脂质代谢分别发生了极大的改变。此外，肝硬化中炎症的增强与碳水化合物代谢向脂质和氨基酸代谢的转变有关。在患病小鼠肝脏中发现的差异表达的代谢产物中，D-葡萄糖和D-甘露醇显示出最显著的变化，突出了它们作为肝细胞癌发展的潜在早期诊断生物标志物。总之，这些对肝细胞癌癌前阶段发生的动态代谢变化的研究增加并完善了对慢性炎症最终如何导致癌症的理解。此外，这些发现为鉴定可能作为这些展开事件的早期诊断指标的代谢物奠定了基础。(C)2015爱思唯尔有限公司版权所有。
The observation that prolonged inflammation plays a causative role in cancer development has been well documented. However, an incremental process that leads from healthy to malignant phenotypes has not yet been described. Experimentally induced hepatocellular carcinoma is considered one of the representative laboratory models for studying this process. Hepatic exposure to viral infection or toxic reagents leads to chronic inflammation and gradual transformation into hepatocellular carcinoma. Here we present metabolomic profiles of hepatic cells at different stages during inflammation-induced cellular transformation by N-nitrosodiethylamine. Using gas chromatography mass spectrometry, we quantitatively assessed the changes in cellular metabolites during the transformation process in hepatitis and liver cirrhosis. Further pathway analysis of the differentially expressed metabolites showed that carbohydrate metabolism and lipid metabolism were greatly altered in hepatitis and liver cirrhosis, respectively. Additionally, the enhanced inflammation in cirrhosis was associated with a shift from carbohydrate metabolism to lipid and amino acid metabolism. Among the differentially expressed metabolites found in diseased mouse livers, D-glucose and D-mannitol showed the most significant changes, highlighting them as potential early-diagnostic biomarkers of hepatocellular carcinoma development. Taken together, these investigations into the dynamic metabolic changes that occur during the precancerous stages of hepatocellular carcinoma add to and refine understanding of how chronic inflammation ultimately leads to cancer. Furthermore, the findings set the stage for identifying metabolites that may serve as early-diagnostic indicators of these unfolding events. (C) 2015 Elsevier Ltd. All rights reserved.