Modulation of steady-state messenger RNA levels in the regenerating rat liver with bile acid feeding

Liver regeneration after two thirds partial hepatectomy (PH) is an orchestr ated hyperplastic growth process requiring coordinated expression of many g enes. The synchronous progression of 95% of the remnant hepatocytes through the cell cycle provides an in vivo model for examining the influence of bi le acids on the molecular regulation of hepatocyte replication and growth, In this study, we examined the effects of endogenous deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) on messenger RNA (mRNA) expression and gro wth rate during liver regeneration, Rats were fed diets containing no addit ion, 0.4% DCA, UDCA, or both for 14 days; they then underwent 70% PH and we re maintained on the diets for an additional 14 days. mRNA transcript level s for a variety of cell cycle-regulated genes were examined post-PH by Nort hern blot analysis, Bile acid concentrations were determined in liver, isol ated nuclei, and plasma by gas chromatography and mass spectrometry, The re sults indicated that the addition of DCA and UDCA to the diet markedly shif ted the bile-acid compositions of liver and plasma. In addition, DCA dramat ically altered the abundance of many transcripts post-PH, whereas coadminis tration of UDCA suppressed the effect, DCA feeding significantly inhibited liver growth through day 3; however, by day 8, it induced an approximately 20% increase in mass compared with controls, UDCA-fed, or combination-fed a nimals, UDCA was concentrated greater than 20-fold in nuclei compared with whole liver in controls and DCA-fed animals and greater than 2-fold with UD CA feeding, These data suggest that bile acids may have a key role in liver regeneration, which is significantly altered by modulation of the bile-aci d pool.