Figure 4.

Activation of PXR by TBC stimulates the expression of the intestinal cholesterol transporter NPC1L1 in mice and increases cholesterol uptake by murine intestinal cells. A, WT and PXR^−/− mice were treated with vehicle or 10 mg/kg BW TBC daily for 1 week. Total RNA was isolated from small intestine, and the expression levels of indicated genes were measured by qPCR (n = 5–6 per group; *, P < .05). B, Western blot analysis of intestinal NPC1L1 protein levels in control or TBC-treated WT and PXR^−/− mice. The top band indicates glycosylated NPC1L1. C and D, Primary enterocytes isolated from WT and PXR^−/− mice were treated with vehicle control or 10 μM TBC for 3 hours. NPC1L1 mRNA levels were measured by qPCR (n = 3; ***, P < .001), and protein levels were analyzed by Western blot (D). E, Primary enterocytes isolated from WT and PXR^−/− mice were treated with vehicle control or 10 μM TBC for 2 hours, followed by incubation with [³H]cholesterol and TBC for 1 hour. The cellular cholesterol uptake was then measured (n = 3; *, P < .05; and **, P < .01).