CAR-induced hepatomegaly is partially due to YAP signaling.
To further explore the role of YAP in TCPOBOP-induced hepatomegaly,Yap -/- mice were used and treated with TCPOBOP
for 10 days (Figure 4A). The liver/body weight ratio still showed an
increase in TCPOBOP treated Yap -/- mice, but
decreased compared with TCPOBOP-treated WT mice, which suggested that
YAP is only partially involved in CAR activation-induced hepatomegaly
(Figure 4B). A slight shrinkage of liver was noted inYap -/- mice in the treated group compared with
the counterpart in WT mice (Figure 4C).
Serum ALT, AST and ALP indicated no significant difference between the
treatment and vehicle group (Figure S4A). The YAP protein and its
downstream targets together with proliferation-related proteins were
also measured (Figure S4B and S4C). YAP was totally depleted inYap -/- mice, YAP downstream targets CTGF,
ANKRD1 and proliferation-related protein CCND1 were upregulated in
TCPOBOP-treated group both in WT and Yap -/-mice.
Immunohistochemical staining of CTNNB1 and KI67 was conducted revealing
that hepatocyte size in the CV area was still enlarged (Figure 4E and
4F), while the number of KI67+ cells was increased in
the PV area in TCPOBOP-treated Yap -/- mice
(Figure 4G and 4H), but the effect was weaker compared with
TCPOBOP-treated WT mice. CTNNB1 staining in the PV area and KI67
staining in the CV area are shown in Figure S4D and S4E.