Hepatocyte-specific deletion of farnesoid X receptor delays but does not inhibit liver regeneration after partial hepatectomy in mice

• DOI: 10.1002/hep.25918
• Publication Date: 2012-06-22T20:31:50Z
• Authors: Prachi Borude; Genea Edwards; Chad Walesky; Feng Li; Xiaochao Ma; Bo Kong; Grace L. Guo; Udayan Apte
• Keywords: Farnesoid X receptor; Liver Regeneration

Farnesoid X receptor (FXR), the primary bile acid-sensing nuclear receptor, also plays a role in stimulation of liver regeneration. Whole body deletion FXR results significant inhibition regeneration after partial hepatectomy (PHX). is expressed and intestines, recent reports indicate that regulates distinct set genes tissue-specific manner. These data raise question about relative contribution hepatic intestinal regulation We studied PHX hepatocyte-specific knockout (hepFXR-KO) mice over time course 0-14 days. Whereas overall kinetics regrowth hepFXR-KO was unaffected, delay peak hepatocyte proliferation from day 2 to 3 observed compared with Cre(-) control mice. Real-time polymerase chain reaction, western blot co-immunoprecipitation studies revealed decreased cyclin D1 expression association CDK4 PHX, correlating phosphorylation Rb protein delayed cell livers. The exhibited acute fat accumulation following which associated cycle. Further, growth factor-initiated signaling, including AKT, c-myc, extracellular signal-regulated kinase 1/2 pathways, Ultraperformance liquid chromatography/mass spectroscopy analysis acids indicated no difference levels mice.Deletion did not completely inhibit but delays secondary activation.