The constitutive androstane receptor(CAR,NR3I1)belongs to nuclear receptor superfamily.It was reported that CAR agonist TCPOBOP induces hepatomegaly but the underlying mechanism re-mains largely unknown.Yes-associated protein(YAP)is a potent regulator of organ size.The aim of this study is to explore the role of YAP in CAR activation-induced hepatomegaly and liver regeneration.TCPOBOP-induced CAR activation on hepatomegaly and liver regeneration was evaluated in wild-type(WT)mice,liver-specific YAP-deficient mice,and partial hepatectomy(PHx)mice.The results demonstrate that TCPOBOP can increase the liver-to-body weight ratio in wild-type mice and PHx mice.Hepatocytes enlargement around central vein(CV)area was observed,meanwhile hepatocytes proliferation was promoted as evidenced by the increased number of KI67+cells around portal vein(PV)area.The protein levels of YAP and its downstream targets were upregulated in TCPOBOP-treated mice and YAP translocation can be induced by CAR activation.Co-immunoprecipitation results suggested a potential protein-protein interaction of CAR and YAP.However,CAR activation-induced hepatomegaly can still be observed in liver-specific YAP-deficient(Yap-/-)mice.In summary,CAR activation promotes hepatomegaly and liver regeneration partially by inducing YAP translocation and interaction with YAP signaling pathway,which provides new insights to further understand the physiological functions of CAR.