{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T08:53:51Z","timestamp":1790412831110,"version":"4.1.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2019,7,26]],"date-time":"2019-07-26T00:00:00Z","timestamp":1564099200000},"content-version":"am","delay-in-days":221,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2018,12,17]],"date-time":"2018-12-17T00:00:00Z","timestamp":1545004800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2018,12,17]],"date-time":"2018-12-17T00:00:00Z","timestamp":1545004800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:p>Activation of pregnane X receptor (PXR), a nuclear receptor that controls xenobiotic and endobiotic metabolism, is known to induce liver enlargement, but the molecular signals and cell types responding to PXR\u2010induced hepatomegaly remain unknown. In this study, the effect of PXR activation on liver enlargement and cell change was evaluated in several strains of genetically modified mice and animal models. Lineage labeling using AAV\u2010<jats:italic toggle=\"yes\">Tbg<\/jats:italic>\u2010Cre\u2010treated <jats:italic toggle=\"yes\">Rosa26<\/jats:italic>\n                           <jats:sup>EYFP<\/jats:sup> mice or <jats:italic toggle=\"yes\">Sox9\u2010Cre<\/jats:italic>\n                           <jats:sup>ERT<\/jats:sup>, <jats:italic toggle=\"yes\">Rosa26<\/jats:italic>\n                           <jats:sup>EYFP<\/jats:sup> mice was performed and <jats:italic toggle=\"yes\">Pxr<\/jats:italic>\u2010null mice or AAV <jats:italic toggle=\"yes\">Yap<\/jats:italic> short hairpin RNA (shRNA)\u2010treated mice were used to confirm the role of PXR or yes\u2010associated protein (YAP). Treatment with selective PXR activators induced liver enlargement and accelerated regeneration in wild\u2010type (WT) and <jats:italic toggle=\"yes\">PXR<\/jats:italic>\u2010humanized mice, but not in <jats:italic toggle=\"yes\">Pxr<\/jats:italic>\u2010null mice, by increase of cell size, induction of a regenerative hybrid hepatocyte (HybHP) reprogramming, and promotion of hepatocyte and HybHP proliferation. Mechanistically, PXR interacted with YAP and PXR activation induced nuclear translocation of YAP. Blockade of YAP abolished PXR\u2010induced liver enlargement in mice. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>\n                           <jats:italic toggle=\"yes\">: <\/jats:italic>These findings revealed a function of PXR in enlarging liver size and changing liver cell fate by activation of the YAP signaling pathway. These results have implications for understanding the physiological functions of PXR and suggest the potential for manipulation of liver size and liver cell fate.<\/jats:p>","DOI":"10.1002\/hep.30131","type":"journal-article","created":{"date-parts":[[2018,7,26]],"date-time":"2018-07-26T14:55:35Z","timestamp":1532616935000},"page":"343-358","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":97,"title":["Pregnane X Receptor Regulates Liver Size and Liver Cell Fate by Yes\u2010Associated Protein Activation in Mice"],"prefix":"10.1097","volume":"69","author":[{"given":"Yiming","family":"Jiang","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences,Sun Yat\u2010Sen University,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dechun","family":"Feng","sequence":"additional","affiliation":[{"name":"Laboratory 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