Mechanism of NOTCH2 in promoting intrahepatic bile duct development.

Background: The Notch signaling pathway plays a crucial role in intrahepatic bile duct development. Here, we aimed to investigate the effect of the Notch receptor, NOTCH2, on intrahepatic bile duct development to better understand congenital intrahepatic bile duct dysplasia.

Results: Estradiol increased NOTCH2 and its downstream proteins expression, which promoted the differentiation of hepatoblasts into intrahepatic cholangiocytes and the development of intrahepatic bile ducts by upregulating the Notch signaling pathway. NOTCH2 siRNA inhibited the above processes (P < 0.05). There was no significant difference between estradiol and estradiol + non-targeting siRNA groups (P > 0.1).

Conclusions: In conclusion, the activation of the Notch signaling pathway leads to increased NOTCH2 expression, which promotes the differentiation of hepatoblasts into intrahepatic cholangiocytes and the development of intrahepatic bile ducts during embryonic stages in C57BL/6CrSlc mice. The results of this study may provide a theoretical basis for infantile intrahepatic cholestasis treatment.