Pregnane X receptor is essential for normal progression of liver regeneration

Guoli Dai, Lin He, Pengli Bu, Yu-Jui Yvonne Wan

Research output: Contribution to journalArticle

80 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1277-1287
Number of pages11
JournalHepatology
Volume47
Issue number4
DOIs
StatePublished - Apr 2008
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology

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