Pregnane X receptor is essential for normal progression of liver regeneration
Open Access
- 31 December 2007
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hepatology
- Vol. 47 (4), 1277-1287
- https://doi.org/10.1002/hep.22129
Abstract
Pregnane X receptor (PXR) mediates xenobiotic and endobiotic metabolism as well as hepatocyte proliferation. To determine the role of PXR in liver regeneration, 2/3 partial hepatectomy (PH) was performed on wild-type and PXR-null mice. Our results showed that hepatic steatosis was markedly suppressed in mice lacking PXR 36 hours after PH, concomitant with reduction of hepatocyte proliferation at the same time point. Gene expression analysis revealed the role of PXR in regulating the transcription of genes involved in lipid uptake, transport, biosynthesis, oxidation, and storage during liver regeneration. When PXR was absent, the second wave of hepatocyte proliferation was severely suppressed, which was accompanied by the inactivation of STAT3. Lack of PXR inhibited the second phase of liver growth, leading to 17% less liver mass at the anticipated end point of liver regeneration (day 10). Conclusion: PXR is required for normal progression of liver regeneration by modulating lipid homeostasis and regulating hepatocyte proliferation. (HEPATOLOGY 2008.)Keywords
This publication has 49 references indexed in Scilit:
- Liver regenerationJournal of Cellular Physiology, 2007
- Nuclear Receptor-Dependent Bile Acid Signaling Is Required for Normal Liver RegenerationScience, 2006
- Mechanisms of liver regeneration and their clinical implicationsJournal of Hepato-Biliary-Pancreatic Surgery, 2005
- Steatosis: Co-factor in other liver diseasesHepatology, 2005
- Disruption of hepatic adipogenesis is associated with impaired liver regeneration in miceHepatology, 2004
- Impaired liver regeneration after partial hepatectomy in db/db miceExperimental and Toxicologic Pathology, 2003
- The hepatocyte is a direct target for transforming-growth factor β activation via the insulin-like growth factor II/mannose 6-phosphate receptorJournal of Hepatology, 2003
- Delayed liver regeneration in peroxisome proliferator-activated receptor-α-null miceHepatology, 2002
- What does Stat3 do?JCI Insight, 2002
- Failure of regeneration of the steatotic rat liver: disruption at two different levels in the regeneration pathwayHepatology, 2000