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

Francis R. Weiner, Mark J. Czaja, Marie Adele Giambrone, Shizuko Takahashi, Luis Biempica, Mark A. Zern

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1557-1562
Number of pages6
JournalBiochemistry
Volume26
Issue number6
DOIs
StatePublished - 1987

ASJC Scopus subject areas

  • Biochemistry

Fingerprint Dive into the research topics of 'Transcriptional and Posttranscriptional Effects of Dexamethasone on Albumin and Procollagen Messenger RNAs in Murine Schistosomiasis'. Together they form a unique fingerprint.

  • Cite this

    Weiner, F. R., Czaja, M. J., Giambrone, M. A., Takahashi, S., Biempica, L., & Zern, M. A. (1987). Transcriptional and Posttranscriptional Effects of Dexamethasone on Albumin and Procollagen Messenger RNAs in Murine Schistosomiasis. Biochemistry, 26(6), 1557-1562. https://doi.org/10.1021/bi00380a010