Asian Science Citation Index is committed to provide an authoritative, trusted and significant information by the coverage of the most important and influential journals to meet the needs of the global scientific community.  
ASCI Database
308-Lasani Town,
Sargodha Road,
Faisalabad, Pakistan
Fax: +92-41-8815544
Contact Via Web
Suggest a Journal
Molecular Endocrinology
Year: 2010  |  Volume: 24  |  Issue: 5  |  Page No.: 886 - 897

FXR Regulates Liver Repair after CCl4-Induced Toxic Injury

Z Meng, Y Wang, L Wang, W Jin, N Liu, H Pan, L Liu, L Wagman, B. M Forman and W. Huang    

Abstract:

Liver repair is key to resuming homeostasis and preventing fibrogenesis as well as other liver diseases. Farnesoid X receptor (FXR, NR1H4) is an emerging liver metabolic regulator and cell protector. Here we show that FXR is essential to promote liver repair after carbon tetrachloride (CCl4)-induced injury. Expression of hepatic FXR in wild-type mice was strongly suppressed by CCl4 treatment, and bile acid homeostasis was disrupted. Liver injury was induced in both wild-type and FXR–/– mice by CCl4, but FXR–/– mice had more severe defects in liver repair than wild-type mice. FXR–/– livers had a decreased peak of regenerative DNA synthesis and reduced induction of genes involved in liver regeneration. Moreover, FXR–/– mice displayed increased mortality and enhanced hepatocyte deaths. During the early stages of liver repair after CCl4 treatment, we observed overproduction of TNF and a strong decrease of phosphorylation and DNA-binding activity of signal transducer and activator of transcription 3 in livers from FXR–/– mice. Exogenous expression of a constitutively active signal transducer and activator of transcription 3 protein in FXR–/– liver effectively reduced hepatocyte death and liver injury after CCl4 treatment. These results suggest that FXR is required to regulate normal liver repair by promoting regeneration and preventing cell death.

View Fulltext    |   Related Articles   |   Back
   
 
 
 
  Related Articles

No Article Found
 
 
 
Copyright   |   Desclaimer   |    Privacy Policy   |   Browsers   |   Accessibility