Vitamin K2-Enhanced Liver Regeneration is Associated with Oval Cell Expansion and Up-Regulation of Matrilin-2 Expression in 2- AAF/PH Rat Model
Normal liver has a great potential of regenerative capacity after partial hepatectomy. In clinic,
however, most patients receiving partial hepatectomy are usually suffering from chronic liver diseases with
severely damaged hepatocyte population. Under these conditions, activation of hepatic progenitor cell (oval
cell in rodents) population might be considered as an alternative mean to enhance liver functional recovery.
Vitamin K2 has been shown to promote liver functional recovery in patients with liver cirrhosis. In this study, we
explored the possibility of vitamin K2 treatment in activating hepatic oval cell for liver regeneration with the
classic 2-acetamido-fluorene/partial hepatectomy (2-AAF/PH) model in Sprague-Dawley rats. In 2-AAF/PH
animals, vitamin K2 treatment induced a dose-dependent increase of liver regeneration as assessed by the
weight ratio of remnant liver versus whole body and by measuring serum albumin level. In parallel, a drastic
expansion of oval cell population as assessed by anti-OV6 and anti-CK19 immunostaining was noticed in the
periportal zone of the remnant liver. Since matrilin-2 was linked to oval cell proliferation and liver regeneration
after partial hepatectomy, we assessed its expression at both the mRNA and protein levels. The results
revealed a significant increase after vitamin K2 treatment in parallel with the expansion of oval cell population.
Consistently, knocking down matrilin-2 expression in vivo largely reduced vitamin K2-induced liver
regeneration and oval cell proliferation in 2-AAF/PH animals. In conclusion, these data suggest that vitamin K2
treatment enhances liver regeneration after partial hepatectomy, which is associated with oval cell expansion
and matrilin-2 up-regulation.
Keywords: Liver regeneration, matrilin-2, oval cell, partial hepatectomy, vitamin K2.
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