S. Kliewer

Publications234
h-index111
Citations63,780
Highly Influential Citations3,330
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The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions.
TLDR
The identification of a human (h) orphan nuclear receptor, termed the pregnane X receptor (PXR), that binds to a response element in the CYP3A4 promoter and is activated by a range of drugs known to induce CYP 3A4 expression is reported. Expand
A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis.
TLDR
A potent, nonsteroidal FXR ligand is used to show that FXR induces expression of small heterodimer partner 1 (SHP-1), an atypical member of the nuclear receptor family that lacks a DNA-binding domain that provides a molecular basis for the coordinate suppression of CYP7A1 and other genes involved in bile acid biosynthesis. Expand
An Orphan Nuclear Receptor Activated by Pregnanes Defines a Novel Steroid Signaling Pathway
TLDR
The results provide evidence for the existence of a novel steroid hormone signaling pathway with potential implications in the regulation of steroid hormone and sterol homeostasis and the expression of the CYP3A family of steroid hydroxylases and modulates sterol and bile acid biosynthesis in vivo. Expand
Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis.
TLDR
It is demonstrated that fibroblast growth factor 15 signals from intestine to liver to repress the gene encoding cholesterol 7alpha-hydroxylase (CYP7A1), which catalyzes the first and rate-limiting step in the classical bile acid synthetic pathway. Expand
The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity
TLDR
It is proposed that PXR serves as a physiological sensor of LCA, and coordinately regulates gene expression to reduce the concentrations of this toxic bile acid, and suggest that PxR agonists may prove useful in the treatment of human cholestatic liver disease. Expand
Bile acids: natural ligands for an orphan nuclear receptor.
TLDR
Results provide evidence for a nuclear bile acid signaling pathway that may regulate cholesterol homeostasis and modulated interaction of FXR with a peptide derived from steroid receptor coactivator 1. Expand
Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21.
TLDR
These findings demonstrate an unexpected role for the PPARalpha-FGF21 endocrine signaling pathway in regulating diverse metabolic and behavioral aspects of the adaptive response to starvation. Expand
Orphan Nuclear Receptors Constitutive Androstane Receptor and Pregnane X Receptor Share Xenobiotic and Steroid Ligands*
TLDR
It is demonstrated that several of the compounds that regulate mouse and human CAR, including natural steroids, bind directly to the receptors and suggest that CAR, like PXR, is a steroid receptor that is capable of recognizing structurally diverse compounds. Expand
Regulation of Multidrug Resistance-associated Protein 2 (ABCC2) by the Nuclear Receptors Pregnane X Receptor, Farnesoid X-activated Receptor, and Constitutive Androstane Receptor*
TLDR
It is demonstrated that MRP2 is regulated by three distinct nuclear receptor signaling pathways that converge on a common response element in the 5′-flanking region of this gene. Expand
An Antidiabetic Thiazolidinedione Is a High Affinity Ligand for Peroxisome Proliferator-activated Receptor γ (PPARγ) (*)
TLDR
It is reported that thiazolidinediones are potent and selective activators of peroxisome proliferator-activated receptor γ (PPARγ), a member of the nuclear receptor superfamily recently shown to function in adipogenesis, and raised the intriguing possibility that PPARγ is a target for the therapeutic actions of this class of compounds. Expand
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