RT Journal Article
ID 76dce0283818560d
A1 Moore, John T.
A1 Goodwin, Bryan
A1 Willson, Timothy M.
A1 Kliewer, Steven A.
T1 Nuclear Receptor Regulation of Genes Involved in Bile Acid Metabolism
JF Critical Reviews™ in Eukaryotic Gene Expression
JO CRE
YR 2002
FD 2002-04-01
VO 12
IS 2
OP 17
AB Over the past few decades, the nuclear receptor superfamily of transcription factors has provided many opportunities for therapeutic intervention in a variety of pathophysiological conditions. A major question now is how many additional drug targets can be identified within this class of proteins. Advances in differential gene expression (DGE) technologies allow powerful new approaches to answer this question. Although DGE analysis is but one of several modern approaches to target identification, it is especially pertinent for nuclear receptors because many of these proteins are ligand-regulated transcription factors that directly alter gene expression. This article will focus on recent DGE experiments that have elucidated the physiological role of nuclear receptors in regulation of the bile acid biosynthesis, transport, and metabolism in the liver. Of particular relevance is the role of nuclear receptors in regulating <i>CYP7A1</i> because this gene encodes the enzyme controlling the first and rate-limiting step in cholesterol degradation to bile acids. Modulation of <i>CYP7A1</i> expression could provide a therapeutic benefit for multiple disease conditions. This article will focus on the relative contributions of farnesoid X-activated receptor, liver receptor homologous protein-1, small heterodimer partner, pregnane X receptor, and liver X receptor to the regulation of this specific gene, and bile acid metabolism in general. These studies highlight the dynamic interplay between nuclear receptors in the regulation of specific metabolic pathways.
PB Begell House
LK https://www.dl.begellhouse.com/journals/6dbf508d3b17c437,482af3b532f110c7,76dce0283818560d.html