2008
DOI: 10.1002/hep.22129
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Pregnane X receptor is essential for normal progression of liver regeneration†

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 invo… Show more

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Cited by 101 publications
(78 citation statements)
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“…Any physiological/pathophysiological role of induction of GADD45␤ and activation of p38 MAPK signal pathway by PXR in the liver remains virtually unexplored at the present time. Our present findings may have provided new insights into understanding the molecular mechanisms by which therapeutics causes various cell signal responses such as hepatomegaly, cell proliferation, apoptosis, and migration, thereby affecting human susceptibility to therapeutic exposures (7,36).…”
Section: Discussionmentioning
confidence: 95%
“…Any physiological/pathophysiological role of induction of GADD45␤ and activation of p38 MAPK signal pathway by PXR in the liver remains virtually unexplored at the present time. Our present findings may have provided new insights into understanding the molecular mechanisms by which therapeutics causes various cell signal responses such as hepatomegaly, cell proliferation, apoptosis, and migration, thereby affecting human susceptibility to therapeutic exposures (7,36).…”
Section: Discussionmentioning
confidence: 95%
“…PXR is also involved in liver repair and lipid and glucose metabolism. 22,23 Furthermore, CAR and PXR coordinate with each other as xenobiotics sensors and regulates expression of cytochrome P450 enzymes and detoxification of xenobiotics. 24 The functional overlapping and crosstalk of these two nuclear receptors have been systematically analyzed and reviewed.…”
Section: Discussionmentioning
confidence: 99%
“…At organ/tissue levels however, PXR may regulate the growth of cell/tissues through different mechanisms. Wan and colleagues reported the mouse lacking PXR showed decreased liver regeneration after partial hepatectomy and the PXR-regulated lipid homoeostasis, which fuels the liver regeneration, may have a role in the suppressed liver growth (Dai et al, 2008). Verma et al (2009) reported that PXR activation induced apoptosis in breast cancer cell line and PXR is anti-proliferative and the effect is mechanistically dependant on the local production of NO and NO-dependent upregulation of p53.…”
Section: Discussionmentioning
confidence: 99%
“…It was found that PXR-null mice showed impaired hepatocyte proliferation after partial hepatectomy suggesting that PXR is required for normal progression of liver regeneration by modulating hepatocyte proliferation (Dai et al, 2008).…”
mentioning
confidence: 99%