ABSTRACT
The constitutive androstane receptor (CAR, NR3I1) belongs to nuclear receptor superfamily. It was reported that CAR agonist TCPOBOP induces hepatomegaly but the underlying mechanism remains 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
ABSTRACT
BACKGROUND:Embryonic stem cel s have the capacity of multi-differentiation potential, and have been utilized for the therapy of acute liver injury. However, the migration and proliferation of embryonic stem cel s after transplantation remains not wel characterized. OBJECTIVE:To track the transplanted embryonic stem cel s in repairing acute liver injury by bioluminescence imaging technology. METHODS:Murine embryonic stem cel s (D3) were transducted with a construct composed of firefly luciferase, monomeric red fluorescence protein and herpes simplex virus truncated thymidine kinase triple fusion reporter genes by lentivirus system. Stable D3 embryonic stem cel s integrating three report genes were screened. The undifferentiated embryonic stem cel s or differentiated embryonic stem cel s from the 6-day-old embryoid body were transplanted into acute liver injury model of SV129 mouse through spleen, and the transplanted cel s were monitored by bioluminescence imaging technology. RESULTS AND CONCLUSION:Reverse transcription PCR results showed that the expression level of Oct-4 and Nanog was not affected in embryonic stem cel s transducted with triple fusion reporter gene compared with wild-type embryonic stem cel s. The migration process of transplanted cel s was visualized by bioluminescence imaging technology. Teratomas were found in both triple fusion-embryonic stem cel s treatment group and triple fusion-embryoid body cel s treatment group at liver, and the teratoma formation could be suppressed by ganciclovir administration because ganciclovir can react with herpes simplex virus truncated thymidine kinase and trigger cel necrosis process. Histological analysis showed that teratomas comprised tissues from al three germ layers. These results demonstrate that triple gene fusion does not affect differentiation potential of embryonic stem cel s and it is risky to utilize embryonic stem cel s for cel therapy, because it affects repair of liver injury. The therapy strategy requires further improvement and real-time visualizing of embryonic stem cel s in vivo is absolutely necessary.