Increased type I procollagen mRNA levels and in vitro protein synthesis in the baboon model of chronic alcoholic liver disease

Abstract

We have investigated the molecular mechanisms responsible for the histologic changes induced by ethanol in the baboon model of alcoholic liver disease. Eleven ethanol-fed baboons and their pair-fed controls had histology evaluated and RNA extracted from percutaneous liver biopsy specimens. In 6 of the ethanol-fed animals, fatty liver developed, but no significant differences were found when the RNA from the control and ethanol-fed livers was translated in the reticulocyte lysate system or analyzed with specific cDNA probes. Five of the baboons given ethanol, however, developed significant fibrosis. Molecular evaluation revealed that the RNA from these livers was more active in in vitro protein synthesis, and the type I procollagen mRNA content was significantly higher per microgram of liver RNA as determined by hybridization analysis (183% ± 23% SEM of control, p < 0.02). In addition, there were higher levels of albumin mRNA content in the livers of ethanol-fed baboons that developed fibrosis (180% ± 21% SEM of control, p < 0.05). There was no change, however, in the levels of β-actin mRNA, a representative constitutive protein. These findings in the baboon model of alcoholic fibrosis show that ethanol consumption (a) increases type I procollagen mRNA, which may foster fibrogenesis; (b) increases albumin mRNA content without causing an increase in serum albumin; and (c) induces no change in levels of β-actin mRNA. These studies also show that percutaneous needle biopsy can supply sufficient tissue to evaluate molecular changes in human liver disease.