Therapeutic approaches for biliary dysgenesis of the PCK rat, an animal model of Caroli's disease with congenital hepatic fibrosis

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Using the PCK rat, an animal model of Caroli's disease with congenital hepatic fibrosis, the involvement of the PI3K/Akt/mTOR pathway in biliary dysgenesis was examined in terms of therapeutic application. NVP-BEZ235 (an inhibitor of PI3K and mTOR) significantly inhibited cell proliferative activity and cystic growth of the cultured PCK cholangiocytes, which was accompanied by inhibition of apoptosis and induction of autophagy in the cells. In vivo, administration of NVP-BEZ235 significantly improved dilatation of intrahepatic bile ducts and liver fibrosis of the PCK rat.