Effect of RXRa agonist bexarotene on gene expression in hepatocytes of hepatic RXRa knockout mice

Retinoid X receptor alpha (RXRa) is a ligand-activated nuclear receptor involved in the regulation of retinoid metabolism. RXRa activation by agonist bexarotene can significantly induce hepatomegaly and promote liver regeneration after 70% partial hepatectomy (PHx) in wild type mice, while these effects were abolished in liver-specific RXRa-knockout mice. However, the underlying mechanisms remain unclear. Our findings reveal that RXRa activation promotes liver proliferation through transactivation of Cyclin D1. These data raise some key questions for understanding the manipulation of liver size and liver regeneration by RXRa agonists. Overall design: RNA-seq profiling of hepatocytes in male flox and hepatic RXRa knockout mice (C57bl/6) treated with 5 days of RXRa agonist bexaratene (100 mg/kg/d, q.d.)