HBV induces different responses of the hepatocytes and oval cells during HBV-related hepatic cirrhosis

Cancer Lett. 2019 Feb 28:443:47-55. doi: 10.1016/j.canlet.2018.11.020. Epub 2018 Nov 29.

Abstract

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.

Keywords: Hepatic cirrhosis; Hepatitis B virus; Hepatocytes; Microarray; Oval cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Proliferation
  • Cross-Sectional Studies
  • Disease Models, Animal
  • Gene Expression Profiling / methods*
  • Gene Regulatory Networks
  • Hepatitis B / genetics*
  • Hepatitis B / metabolism
  • Hepatitis B virus / pathogenicity*
  • Hepatocytes / cytology*
  • Hepatocytes / metabolism
  • Hepatocytes / virology
  • Humans
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / virology
  • Mice
  • Mice, Transgenic
  • Oligonucleotide Array Sequence Analysis