Regulation of albumin and α-fetoprotein gene expression by colloid osmotic pressure in human hepatoma cells

Abstract

Background: Colloid osmotic pressure has been thought to regulate albumin synthesis; however, the exact mechanism remains obscure. In the present study, the effect of colloid osmotic pressure on the albumin and α-fetoprotein gene expression in HuH-7 human hepatoma cells was analyzed. Methods: HuH-7 cells were treated with albumin or dextran (mean mol wt, 70,000), and changes in the levels of albumin and α-fetoprotein messenger RNA (mRNA) were analyzed by Northern blotting. Furthermore, in transient chloramphenicol acetyltransferase (CAT) plasmid transfection experiments, effects of colloid osmotic pressure on CAT activities were studied. Results: By Northern blot analysis, the levels of both albumin and α-fetoprotein mRNA were dose-dependently suppressed by the elevation of colloid osmotic pressure and returned to pretreatment levels 48 hours after the culture medium containing dextran was replaced with a dextran-free fresh medium. In transient CAT plasmid transfection experiments, the increased level of colloid osmotic pressure resulted in the repression of both albumin and α-fetoprotein promoter activities. In contrast, α-fetoprotein enhancer activity, which possibly regulates not only α-fetoprotein but also albumin gene expression, was not affected by changes in colloid osmotic pressure. Conclusions: These results suggest that colloid osmotic pressure regulates both albumin and α-fetoprotein gene transcription through the modulation of their promoter activities.