Summary: | Chronic liver disease is a leading cause of death globally and non-alcoholic fatty liver disease (NAFLD) is put in the spotlight with increasing prevalence. With no effective therapeutics apart from lifestyle modifications and liver transplantation, treatment of NAFLD remains a challenge. As NAFLD is characterised by impaired liver
regeneration capacity which causes eventual liver failure, enhancing hepatocyte
proliferation may ameliorate disease progression. Here, we identified 6 novel gene candidates potentially involved in regulating liver regeneration, through in vivo RNA interference functional genetic screen using small hairpin RNA (shRNA). The effect of shRNA-mediated knockdown of the candidates on cell proliferation were
evaluated in vitro. Based on the results, we narrowed down to one candidate, Target 1. Downregulation of Target 1 increased hepatocyte proliferation in vitro and in vivo.
Similar phenotype was also observed in hepatocytes treated with Target 1
antagonist. Our results suggest that Target 1 may be further explored for NAFLD
treatment. We also established an in vitro steatosis model with NAFLD phenotypes –
excessive lipid accumulation and slower cell proliferation. Future studies can be
focused on elucidating mechanism of Target 1 using the steatosis model, to gain
insights into pathways regulating liver regeneration and to identify new therapeutic
targets.
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