Pregnane X receptor is essential for normal progression of liver regeneration.
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).


CONCLUSIONS
PXR is required for normal progression of liver regeneration by modulating lipid homeostasis and regulating hepatocyte proliferation.
Dai
Guoli
G
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA.
He
Lin
L
Bu
Pengli
P
Wan
Yu-Jui Yvonne
YJ
D000818:Animals; D049109:Cell Proliferation; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D015870:Gene Expression; D006498:Hepatectomy; D022781:Hepatocytes / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D050356:Lipid Metabolism / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000254:growth & development / Q000378:metabolism; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000077297:Pregnane X Receptor; D012333:RNA, Messenger / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism
D008565:Membrane Proteins; D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D011987:Receptors, Steroid; D050796:STAT3 Transcription Factor; C496508:Cyp3a11 protein, mouse; D051544:Cytochrome P-450 CYP3A