Transcriptional and Posttranscriptional Effects of Dexamethasone on Albumin and Procollagen Messenger RNAs in Murine Schistosomiasis

We have previously shown that dexamethasone increases albumin mRNA and decreases procollagen steady-state mRNA levels in rat hepatocyte cultures. These studies were extended by evaluating an in vivo model of fibrogenesis (murine schistosomiasis) and by determining a more precise level of gene expression responsible for these changes. Control mice and litter mates infected with Schistosomiasis mansoni were evaluated at 8 weeks postinfection when the livers of the infected mice had become fibrotic and their serum albumin levels significantly decreased. The addition of 4 μg/mL dexamethasone to the drinking water of half of the infected mice led to a 75% decrease in the liver collagen content as determined by highperformance liquid chromatography. RNA was extracted from the livers of mice under three conditions: control and infected ± dexamethasone. This RNA was then hybridized with cDNA probes to determine steady-state levels of specific mRNAs. In the infected mice, albumin mRNA levels were decreased compared to control; however, infected mice treated with dexamethasone increased their albumin mRNA content by 3-fold at 8 weeks. Types I and IV procollagen steady-state mRNA levels in infected mice were increased compared to control while dexamethasone suppressed the mRNA level of collagen in infected mice by 50%. The level of gene expression responsible for these steady-state changes was evaluated by nuclear run-on analysis. While the effect of schistosomiasis on these genes was primarily at a transcriptional level, dexamethasone exerted its effect on different genes in the injured liver by diverse mechanisms, i.e., decreasing collagen synthesis at a transcriptional level and increasing albumin by posttranscriptional mechanisms. Corticosteroid-induced changes appear to lead to a stabilization of liver function and inhibition of fibrogenesis. This may explain why corticosteroids are beneficial in some forms of chronic liver disease in man.