CAR activation induces hepatomegaly in mice liver.
To evaluate the effect of hepatomegaly induced by CAR, mice were treated
for 5 or 10 days with the CAR specific agonist TCPOBOP (Figure 1A).
Liver/body weight ratios were significantly increased after treated by
TCPOBOP (Figure 1B). Liver morphology also showed an obvious enlargement
both 5 and 10 days after TCPOBOP treatment (Figure 1C). H&E staining
did not reveal significant liver injury (Figure 1D). Serum ALT, AST and
ALP were also examined and there was no significant difference between
the TCPOBOP group and vehicle group (Figure S1A), suggesting that the
hepatomegaly was not induced by liver injury.
It was reported that TCPOBOP can induce hepatocyte proliferation and the
increase hepatocyte cell size (Blanco-Bose et al., 2008). To
characterize the size of hepatocytes, CTNNB1 staining was performed and
an increase of cell size around the central vein (CV) area was observed
(Figure 1E and 1F), while there was no significant change in cell size
around the portal vein (PV) area (Figure S1B). Expression of KI67 was
determined by immunohistochemistry to assess hepatocyte proliferation.
The number of KI67+ cells around the PV area was
dramatically increased after 5 or 10 days of TCPOBOP treatment,
indicating a high level of cell proliferation induced by CAR (Figure 1G
and 1H). However, the KI67+ cells did not appear
around the CV area (Figure S1C).