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).