Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
Cancer Lett. 2019 Feb 28;443:47-55. doi: 10.1016/j.canlet.2018.11.020. Epub 2018 Nov 29.
Although hepatitis B virus (HBV)-related cirrhosis and hepatocellular carcinoma (HCC) cause a sever health problem worldwide, the underlying mechanisms are still elusive. This study aimed to investigate the responses of different cell types isolated from HBV transgenic mice. A cross-sectional set of hepatocytes and oval cells were obtained from HBV transgenic and control mice. Flow cytometry, immunohistochemistry and microarray were applied to investigate the cell biology of the hepatocytes and oval cells. Our results showed that HBV induced the proliferation of both cell oval cells and hepatocytes, and induced cell death of HBV hepatocytes while had minimal effects on oval cells. Further molecular and pathways analysis identified some genes and signaling pathways may be responsible for the different responses between oval cells and hepatocytes. In addition, analyses of selectively ten genes by IHC staining in human samples were consistent with microarray data. In summary, HBV transgenic mice is a useful model for studying the biological behaviors of oval cells affected by HBV and HBV-cirrhosis. Also, our results help better understand the mechanisms of HBV induced cirrhosis, and provide novel progenitor markers or prognostic/therapeutic markers.
尽管乙型肝炎病毒(HBV)相关的肝硬化和肝细胞癌(HCC)在全球范围内造成了严重的健康问题,但其潜在机制仍不清楚。本研究旨在研究从乙型肝炎病毒转基因小鼠中分离出的不同细胞类型的反应。从 HBV 转基因和对照小鼠中获得了一组横断的肝细胞和卵圆细胞。应用流式细胞术、免疫组织化学和微阵列分析来研究肝细胞和卵圆细胞的细胞生物学。我们的结果表明,HBV 诱导了两种细胞(卵圆细胞和肝细胞)的增殖,并诱导了 HBV 肝细胞的细胞死亡,而对卵圆细胞的影响很小。进一步的分子和途径分析确定了一些基因和信号通路可能负责卵圆细胞和肝细胞之间的不同反应。此外,对人类样本中十个基因的选择性分析通过 IHC 染色与微阵列数据一致。总之,HBV 转基因小鼠是研究受 HBV 和 HBV 肝硬化影响的卵圆细胞的生物学行为的有用模型。此外,我们的结果有助于更好地理解 HBV 诱导肝硬化的机制,并提供新的祖细胞标记物或预后/治疗标记物。