Proteomic and transcriptomic studies of HBV-associated liver fibrosis of an AAV-HBV-infected mouse model.
Proteomic and transcriptomic studies of HBV-associated liver fibrosis of an AAV-HBV-infected mouse model.
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AAV-HBV感染的小鼠模型的HBV相关肝纤维化的蛋白质组学和转录组研究。
DOI：
10.1186/s12864-017-3984-z
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发表时间：
2017-08-22
期刊：
影响因子：
4.4
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Kan F;Ye L;Yan T;Cao J;Zheng J;Li W
人类B型肝炎病毒（HBV）感染是亚太地区重要的公共卫生问题，与慢性肝炎、肝纤维化、肝硬化甚至肝癌有关。然而，HBV相关性肝纤维化的潜在机制仍不完全清楚。在本研究中，蛋白质组学和转录组学的方法以及生物网络分析进行了研究差异表达的分子特征和关键调控网络，与HBV介导的肝纤维化。对从通过AAV 8-HBV病毒产生的HBV感染的C57 BL/6小鼠获得的肝组织样品进行RNA测序和2DE-MALDI-TOF/TOF。结果表明，322个基因和173个蛋白质差异表达，并通过综合蛋白质组学和转录组学分析确定了28个HBV特异性蛋白质。GO分析表明，差异表达的蛋白质主要涉及氧化应激，而氧化应激在HBV相关的肝纤维化中发挥关键作用。重要的是，CAT，PRDX 1，GSTP 1，NXN和BLVRB被证明与氧化应激的差异表达蛋白。通过Western印迹和RT-qPCR验证了最显著的结果。RIG-I样受体信号通路被认为是HBV相关纤维化过程中发生变化的主要信号通路。这项研究为HBV相关的肝纤维化提供了新的见解，并揭示了氧化应激在肝纤维化中的重要作用。此外，CAT、BLVRB、NXN、PRDX 1和IDH 1可能是用于检测肝纤维化或用于治疗肝纤维化的治疗靶标的候选物。本文的在线版本（doi：10.1186/s12864-017-3984-z）包含补充材料，可供授权用户使用。
Human hepatitis B virus (HBV) infection is an important public health issue in the Asia-Pacific region and is associated with chronic hepatitis, liver fibrosis, cirrhosis and even liver cancer. However, the underlying mechanisms of HBV-associated liver fibrosis remain incompletely understood. In the present study, proteomic and transcriptomic approaches as well as biological network analyses were performed to investigate the differentially expressed molecular signature and key regulatory networks that were associated with HBV-mediated liver fibrosis. RNA sequencing and 2DE-MALDI-TOF/TOF were performed on liver tissue samples obtained from HBV-infected C57BL/6 mouse generated via AAV8-HBV virus. The results showed that 322 genes and 173 proteins were differentially expressed, and 28 HBV-specific proteins were identified by comprehensive proteomic and transcriptomic analysis. GO analysis indicated that the differentially expressed proteins were predominantly involved in oxidative stress, which plays a key role in HBV-related liver fibrosis. Importantly, CAT, PRDX1, GSTP1, NXN and BLVRB were shown to be associated with oxidative stress among the differentially expressed proteins. The most striking results were validated by Western blot and RT-qPCR. The RIG-I like receptor signaling pathway was found to be the major signal pathway that changed during HBV-related fibrosis. This study provides novel insights into HBV-associated liver fibrosis and reveals the significant role of oxidative stress in liver fibrosis. Furthermore, CAT, BLVRB, NXN, PRDX1, and IDH1 may be candidates for detection of liver fibrosis or therapeutic targets for the treatment of liver fibrosis. The online version of this article (doi:10.1186/s12864-017-3984-z) contains supplementary material, which is available to authorized users.
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影响因子：
64.5
作者：
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通讯作者：
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影响因子：
3.4
作者：
Ding, Chen;Wei, Haiming;Tian, Zhigang
通讯作者：
Tian, Zhigang