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DOI: 10.1055/s-0037-1612689
Structural and molecular signatures of disease progression from NASH to HCC in mouse model and human
Publication History
Publication Date:
03 January 2018 (online)
Background and aims:
Non-alcoholic fatty liver disease (NAFLD) is characterized by steatosis and in advanced stages, inflammation which is frequently accompanied by organ fibrosis (non-alcoholic steatohepatitis, NASH) and eventually hepatocellular carcinoma (HCC). Noteworthy, a considerable fraction of patients may suffer from progression of the disease towards hepatocellular carcinoma (HCC). Therefore, we aim to identify cellular, structural and molecular signatures associated with NAFLD/NASH progression to HCC.
Methods:
A NASH-based hepatocellular carcinoma model (STAM) was performed. In this model, 4 different fatty liver disease stages, namely, steatosis, steatohepatitis, fibrosis and HCC were analysed. Both histopathological and Affymetrix based transcriptomics characterizations were achieved.
Result:
Using HistoCad tool, we were able to show that steatosis was started at 6 week age mice and progressed in time to HCC. Fibrosis was evaluated by Sirius red and alpha-SMA staining for collagen and collagen producing cells, respectively. Moreover, resident macrophages were visualized by F4/80 staining showing accumulation of F4/80 cells in a close proximity of steatotic cells. Bioinformatic amaylsis of transcriptomics revealed that 1500 – 3500 genes were deregulated in different disease stages including several pathways e.g. lipid metabolism.
Conclusion:
We can conclude that a STAM mouse is an optimal model to study NASH-based HCC for diagnostic and therapeutical studies. Further, the comparative analysis between different stages of NASH and HCC using this mouse model and human patients will be achieved in the near future.