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 micrograms/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 high-performance 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.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D003094:Collagen / Q000235:genetics; D004247:DNA / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009693:Nucleic Acid Hybridization; D011347:Procollagen / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics*; D012555:Schistosomiasis mansoni / Q000378:metabolism* / Q000473:pathology; D012709:Serum Albumin / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*
D011347:Procollagen; D012333:RNA, Messenger; D012709:Serum Albumin; D003907:Dexamethasone; D003094:Collagen; D004247:DNA