Sustainable inflammation transforms hepatic cells by causing oxidative stress injury and potential epithelial-mesenchymal transition.
Sustainable inflammation transforms hepatic cells by causing oxidative stress injury and potential epithelial-mesenchymal transition.
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持续的炎症通过引起氧化应激损伤和潜在的上皮间质转化来改变肝细胞。
DOI：
10.3892/ijo.2016.3580
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发表时间：
2016-09
影响因子：
5.2
通讯作者：
Shi Songlin
中科院分区：
文献类型：
--
作者：
Lu Kun;Liu Guoyan;Yang Ling;Liu Fan;Gao Libin;Shi Jingxian;Deng Xiaoling;Li Qifu;Xu Donghui;Shi Songlin
炎症微环境促进肿瘤发生。然而，通过炎症转化癌前病变中的肝细胞的机制仍不清楚。肝细胞在癌变前发生代谢的显著变化，但癌前炎症反应中基因表达和细胞功能的特异性改变尚未阐明。本研究成功建立了肝炎-肝癌小鼠模型。然后进行无标记定量（LFQ）蛋白质组学结合生物信息学分析，以确定差异表达的蛋白质及其在肝细胞癌前炎症中的功能。我们发现，不同的化学处理诱导模型中的几个常见的变化。肝细胞受到严重的氧化应激损伤。使用IPA的典型途径分析揭示了信号传导途径的激活，例如整联蛋白信号传导、Rho家族GTP酶的信号传导、IL-8信号传导和ILK信号传导，以及RhoGDI信号传导的抑制。对KEGG通路的分析表明，粘着斑和调节肌动蛋白细胞骨架的通路发生了改变。蛋白质印迹分析的结果表明，包括p-STAT 3、TWIST、SNAIL、波形蛋白和MMP-9在内的蛋白质上调，这些蛋白质参与上皮-间质转化（EMT）。这些结果表明，肝细胞可能经历EMT。有趣的是，E-cadherin的表达上调，但这一观察必须进一步研究。总之，结果表明，在肝脏癌前炎症阶段发生了显着的功能和途径变化。本研究有助于进一步认识炎症在肝癌发生中的作用，为进一步研究肝癌的发生机制提供了分子基础。
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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影响因子：
64.5
作者：
Hatziapostolou M;Polytarchou C;Aggelidou E;Drakaki A;Poultsides GA;Jaeger SA;Ogata H;Karin M;Struhl K;Hadzopoulou-Cladaras M;Iliopoulos D
通讯作者：
Iliopoulos D
影响因子：
2.8
作者：
Figel, Sheila;Gelman, Irwin H.
通讯作者：
Gelman, Irwin H.
影响因子：
78.5
作者：
M. Poirier
通讯作者：
M. Poirier
DOI：
10.1111/j.1749-6632.2009.03704.x
发表时间：
2009-01-01
期刊：
STEROID ENZYMES AND CANCER
影响因子：
--
作者：
Berasain, C.;Castillo, J.;Avila, M. A.
通讯作者：
Avila, M. A.
影响因子：
5.5
作者：
Zhao XR;Gonzales N;Aronowski J
通讯作者：
Aronowski J