Overexpression of NK2 inhibits liver regeneration after partial hepatectomy in mice

Figure 1 Cumulative survival after PH. Survival of WT mice (n = 23, open circles) and NK2 transgenic mice (n = 21, closed circles) after PH. The survival rate was significantly low in NK2 transgenic mice (^bP<0.01 vs WT mice).

Figure 2 Liver regeneration and proliferation of hepatocytes after PH. H-E stain of WT mouse liver (A) and NK2 transgenic mouse liver (B) at 48 h after PH. NK2 transgenic mouse liver contained a large amount of intracellular small droplets. Magnification, ×200. Oil-red-O stain of NK2 transgenic mouse liver (C) at 48 h after PH. Note the presence of many small lipid droplets in hepatocytes. Magnification, ×400. BrdU stain of WT mouse liver (D) and NK2 transgenic mouse liver (E) at 48 h after PH. The arrows show hepatocytes undergoing DNA synthesis. Magnification, ×100. The BrdU labeling index of WT mice and NK2 transgenic mice at 48 h after PH (n = 30 per group). (F) Data are mean±SD of the mean. Hepatocyte proliferation was significantly reduced in NK2 transgenic mouse liver (^bP<0.01 vs WT mouse liver).

Figure 3 Expressions of RNAs and proteins of transgene and c-Met after PH. RNA expression of transgenic NK2 and c-Met, and c-Met protein levels and activity in livers from WT and NK2 transgenic mice after PH. Lane 1, WT mouse before PH; lane 2, WT mouse at 48 h after PH; lane 3, NK2 transgenic mouse before PH; lanes 4 and 5, dying NK2 transgenic mice at 48 h after PH; lanes 6 and 7, healthy NK2 transgenic mice at 48 h after PH. (A) Each RNA sample was subjected to Northern blot analysis. Expression levels of all transgenes were high at each time point and endogeneous c-Met expression was unaltered in each group. β-actin RNA expression was also examined as a control. (B) Each protein sample was subjected to IP and then IB with an anti c-Met antibody or an anti PY antibody. c-Met expression and the kinase activity were unaltered in each group.

Figure 4 RNA expression of TNF-α and IL-6 after PH. TNF-α mRNA and IL-6 mRNA expression in livers of WT mice and NK2 transgenic mice. Lane 1, WT mouse before PH; lane 2, NK2 transgenic mouse before PH; lanes 3 and 4, WT mice at 48 h after PH; lanes 5 and 6, dying NK2 transgenic mice at 48 h after PH; lanes 7 and 8, healthy NK2 transgenic mice at 48 h after PH. The expression of TNF-α mRNA was increased in NK2 transgenic mice that died at 48 h after PH. IL-6 mRNA expression was detected in NK2 transgenic mice that died at 48 h after PH. β-actin mRNA expression was also examined as a control.