Altered circadian rhythm of the clock genes in fibrotic livers induced by carbon tetrachloride

FEBS Lett. 2010 Apr 16;584(8):1597-601. doi: 10.1016/j.febslet.2010.03.019. Epub 2010 Mar 15.


Disruption in circadian rhythms either by mutation in mice or by shiftwork in people, is associated with an increased risk for the development of multiple organ diseases. In turn, organ disease may influence the function of clock genes and peripheral circadian systems. Here we showed that hepatic fibrosis induced by carbon tetrachloride in mice leads to alterations in the circadian rhythms of hepatic clock genes. Especially, we found an impaired daily Cry2 rhythm in the fibrotic livers, with markedly decreased levels during the day time while compared with control livers. Associatively, the expressions of two important clock-regulated genes peroxisome proliferator-activated receptor alpha and cytochrome P450 oxidoreductase lost circadian rhythm with significantly decreased levels during the light-dark (12/12h) cycle in fibrotic livers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Tetrachloride / pharmacology*
  • Circadian Rhythm / drug effects*
  • Circadian Rhythm / genetics*
  • Gene Expression Regulation / drug effects
  • Hepatic Stellate Cells / drug effects
  • Hepatic Stellate Cells / metabolism
  • Hepatic Stellate Cells / pathology
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis / chemically induced*
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / physiopathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NADPH-Ferrihemoprotein Reductase / genetics
  • PPAR alpha / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Time Factors


  • PPAR alpha
  • RNA, Messenger
  • Carbon Tetrachloride
  • NADPH-Ferrihemoprotein Reductase