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Updated: Oct 20, 2025

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
Metabolic nuclear receptors coordinate energy metabolism to regulate Sox9+ hepatocyte fate
Shenghui Liu1, Dan Qin1, Yi Yan1
1College of Veterinary Medicine/Bio-medical Center, Huazhong Agricultural University, Wuhan, Hu Bei 430070, China.
Abstract:
Recent research has indicated the adult liver Sox9+ cells located in the portal triads contribute to the physiological maintenance of liver mass and injury repair. However, the physiology and pathology regulation mechanisms of adult liver Sox9+ cells remain unknown. Here, PPARα and FXR bound to the shared site in Sox9 promoter with opposite transcriptional outputs. PPARα activation enhanced the fatty acid β-oxidation, oxidative phosphorylation (OXPHOS), and adenosine triphosphate (ATP) production, thus promoting proliferation and differentiation of Sox9+ hepatocytes along periportal (PP)-perivenous (PV) axis. However, FXR activation increased glycolysis but decreased OXPHOS and ATP production, therefore preventing proliferation of Sox9+ hepatocytes along PP-PV axis by promoting Sox9+ hepatocyte self-renewal. Our research indicates that metabolic nuclear receptors play critical roles in liver progenitor Sox9+ hepatocyte homeostasis to initiate or terminate liver injury-induced cell proliferation and differentiation, suggesting that PPARα and FXR are potential therapeutic targets for modulating liver regeneration.
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