Expression and regulation of the bile acid transporter, OSTalpha-OSTbeta in rat and human intestine and liver.
The regulation of the OSTalpha and OSTbeta expression was studied in the rat jejunum, ileum, colon and liver and in human ileum and liver by ligands for the farnesoid X receptor (FXR), pregnane X receptor (PXR), vitamin D receptor (VDR) and glucocorticoid receptor (GR) using precision cut tissue slices. The gradient of protein and mRNA expression in segments of the intestine for rOSTalpha and rOSTbeta paralleled that of rASBT. OSTalpha and OSTbeta mRNA expression, quantified by qRT-PCR, in rat jejunum, ileum, colon and liver, and in human ileum and liver was positively regulated by FXR and GR ligands. In contrast, the VDR ligand, 1,25(OH)2D3 decreased the expression of rOSTalpha-rOSTbeta in rat intestine, but had no effect on human ileum, and rat and human liver slices. Lithocholic acid (LCA) decreased the expression of rOSTalpha and rOSTbeta in rat ileum but induced OSTalpha-OSTbeta expression in rat liver slices, and human ileum and liver slices. The PXR ligand, pregnenolone-16alpha carbonitrile (PCN) had no effect. This study suggest that, apart from FXR ligands, the OSTalpha and OSTbeta genes are also regulated by VDR and GR ligands and not by PXR ligands. This study show that VDR ligands exerted different effects on OSTalpha-OSTbeta in the rat and human intestine and liver compared with other nuclear receptors, FXR, PXR, and GR, pointing to species- and organ-specific differences in the regulation of OSTalpha-OSTbeta genes.
Khan
Ansar A
AA
Pharmacokinetics, Toxicology and Targeting, Department of Pharmacy, University of Groningen, The Netherlands. a.a.khan@rug.nl
Chow
Edwin C Y
EC
Porte
Robert J
RJ
Pang
K Sandy
KS
Groothuis
Geny M M
GM
D000818:Animals; D005455:Fluorescent Antibody Technique; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D008024:Ligands; D008099:Liver / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000096:biosynthesis* / Q000187:drug effects*; D000077297:Pregnane X Receptor; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D018167:Receptors, Calcitriol / Q000187:drug effects; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D011987:Receptors, Steroid / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity; D000099150:Receptor, Farnesoid X-Activated
D008024:Ligands; D026901:Membrane Transport Proteins; D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D018160:Receptors, Cytoplasmic and Nuclear; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D000099150:Receptor, Farnesoid X-Activated; C544003:Slc51a protein, rat; C544004:Slc51b protein, rat; C476575:organic solute transporter alpha, human; C476577:SLC51B protein, human