Sustainable inflammation transforms hepatic cells by causing oxidative stress injury and potential epithelial-mesenchymal transition

  • Authors:
    • Kun Lu
    • Guoyan Liu
    • Ling Yang
    • Fan Liu
    • Libin Gao
    • Jingxian Shi
    • Xiaoling Deng
    • Qifu Li
    • Donghui Xu
    • Songlin Shi
  • View Affiliations

  • Published online on: June 16, 2016     https://doi.org/10.3892/ijo.2016.3580
  • Pages: 971-980
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Abstract

The inflammatory microenvironment promotes tumorigenesis. However, the mechanism through which inflammation transforms hepatic cells in precancerous lesions remains unclear. Hepatic cells undergo significant changes in metabolism before carcinogenesis, but the specific alterations in gene expression and cellular functions in response to precancerous inflammation have not been elucidated. In this study, a hepatitis-hepatoma mouse model was successfully established. Label-free quantitative (LFQ) proteomics coupled with bioinformatics analysis was then performed to identify differentially expressed proteins and their functions in hepatic cells with precancerous inflammation. We found that different chemical treatments induced several common changes in the model. Hepatic cells underwent serious oxidative stress injury. Canonical pathway analysis using IPA revealed the activation of signaling pathways, such as integrin signaling, signaling by Rho family GTPases, IL-8 signaling, and ILK signaling, as well as the inhibition of RhoGDI signaling. Analysis of the KEGG pathway indicated alteration in the pathways for focal adhesion and regulation of actin cytoskeleton. Results from western blot analysis demonstrated the upregulation of proteins, including p-STAT3, TWIST, SNAIL, Vimentin, and MMP-9, which are involved in epithelial-mesenchymal transition (EMT). These results indicated that hepatic cells were likely to undergo EMT. Interestingly, the expression of E-cadherin was upregulated, but this observation must be further investigated. In conclusion, the results revealed that notable functional and pathway changes occurred during the precancerous inflammation stage in the liver. Our study contributes to understanding of the roles of inflammation in tumorigenesis and provides a molecular basis for further studies on the tumorigenesis of hepatocellular carcinoma.
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September 2016
Volume 49 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Lu, K., Liu, G., Yang, L., Liu, F., Gao, L., Shi, J. ... Shi, S. (2016). Sustainable inflammation transforms hepatic cells by causing oxidative stress injury and potential epithelial-mesenchymal transition. International Journal of Oncology, 49, 971-980. https://doi.org/10.3892/ijo.2016.3580
MLA
Lu, K., Liu, G., Yang, L., Liu, F., Gao, L., Shi, J., Deng, X., Li, Q., Xu, D., Shi, S."Sustainable inflammation transforms hepatic cells by causing oxidative stress injury and potential epithelial-mesenchymal transition". International Journal of Oncology 49.3 (2016): 971-980.
Chicago
Lu, K., Liu, G., Yang, L., Liu, F., Gao, L., Shi, J., Deng, X., Li, Q., Xu, D., Shi, S."Sustainable inflammation transforms hepatic cells by causing oxidative stress injury and potential epithelial-mesenchymal transition". International Journal of Oncology 49, no. 3 (2016): 971-980. https://doi.org/10.3892/ijo.2016.3580