Effects of retinoic acid on the development of liver fibrosis produced by carbon tetrachloride in mice

Lan Wang, James John Potter, Lynda Rennie-Tankersley, Gennadiy Novitskiy, Jennifer Sipes, Esteban Mezey

Research output: Contribution to journalArticle

Abstract

The role of retinoic acid (RA) in liver fibrogenesis was previously studied in cultured hepatic stellate cells (HSCs). RA suppresses the expression of α2(I) collagen by means of the activities of specific nuclear receptors RARα, RXRβ and their coregulators. In this study, the effects of RA in fibrogenesis were examined in carbon tetrachloride (CCl4) induced liver fibrosis in mice. Mice were treated with CCl4 or RA and CCl4, along side control groups, for 12 weeks. RA reduced the amount of histologically detectable fibrosis produced by CCl4. This was accompanied by a attenuation of the CCl4 induced increase in α2(I) collagen mRNA and a lower (2-fold versus 3-fold) increase in liver hydroxyproline. Furthermore, RA reduced the levels of 3-nitrotyrosine (3-NT) protein adducts and thiobarbituric acid (TBA) reactive substance (TBARS) in the liver, which are formed as results of oxidative stress induced by CCl4 treatment. These in vivo findings support our previous in vitro studies in cultured HSC of the inhibitory effect of RA on type I collagen expression. The data also provide evidence that RA reduces CCl4 induced oxidative stress in liver, suggesting that the anti-fibrotic role of RA is not limited to the inhibition of type I collagen expression.

Original languageEnglish (US)
Pages (from-to)66-71
Number of pages6
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1772
Issue number1
DOIs
Publication statusPublished - Jan 2007

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Keywords

  • Carbon tetrachloride
  • Collagen
  • Liver fibrosis
  • Oxidative stress
  • Retinoic acid

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Biophysics

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