Mechanisms of CCl4-induced liver fibrosis with combined transcriptomic and proteomic analysis

摘要

The classic toxicity of carbon tetrachloride (CCl₄) is to induce liver lesion and liver fibrosis. Liver fibrosis is a consequence of chronic liver lesion, which can progress into liver cirrhosis even hepatocarcinoma. However, the toxicological mechanisms of CCl₄-induced liver fibrosis remain not fully understood. We combined transcriptomic and proteomic analysis and biological network technology, predicted toxicological targets and regulatory networks of CCl₄ in liver fibrosis. Wistar rats were treated with CCl₄ for 9 weeks. Histopathological changes, hydroxyproline (Hyp) contents, serum ALT and AST in the CCl₄-treated group were significantly higher than that of CCl₄-untreated group. CCl₄-treated and -untreated liver tissues were examined by microarray and iTRAQ. The results showed that 3535 genes (fold change ≥ 1.5, P 4 treatment. Therefore, the toxicological mechanisms of CCl₄-induced liver fibrosis may be related with multi biological process, pathway and targets which may provide potential protection reaction mechanism for CCl₄ detoxication in the liver.