Vitamin D Receptor-dependent Regulation of Colon Multidrug Resistance-associated Protein 3 Gene Expression by Bile Acids

Modulation of Bile Acid Metabolism by 1α-Hydroxyvitamin D3Administration in Mice

“…VDR has dual functions as an endocrine receptor for 1,25(OH) 2 D 3 and as a metabolic sensor for secondary bile acids, such as lithocholic acid (Makishima et al, 2002). Although several genes involved in bile acid metabolism, such as CYP3A4 and MRP3, have been reported to be VDR target genes (McCarthy et al, 2005;Matsubara et al, 2008), the in vivo role of VDR as a bile acid sensor may be limited. Whereas administration of high concentrations of LCA restored serum calcium levels to the normal range in vitamin D-deficient rats by increasing VDR target gene expression and bone calcium mobilization, it was not effective in rats with normal vitamin D levels (Nehring et al, 2007).…”

“…The bile acid transporters Mrp2, Mrp4, and Ost␣/␤ are thought to be involved in urinary bile acid excretion (Zollner et al, 2006a;Alrefai and Gill, 2007). Although the role of Mrp3 in renal bile acid transport has not been elucidated, Mrp3 is a direct target gene of VDR (McCarthy et al, 2005). 1␣(OH)D 3 treatment increased mRNA expression of kidney Mrp2, Mrp3, and Mrp4 (Fig.…”

“…Dehydroepiandrosterone sulfotransferase 2A1, apical sodium-dependent bile acid transporter (Asbt), and multidrug resistance-associated protein (MRP) 3 have been demonstrated to be VDR target genes in mouse and human cells (Echchgadda et al, 2004;McCarthy et al, 2005;Chen et al, 2006). Although these proteins are involved in bile acid metabolism, the in vivo role of VDR in bile acid metabolism has not been elucidated.…”

Intestinal CYP3A4 protects against lithocholic acid-induced hepatotoxicity in intestine-specific VDR-deficient mice

“…7) . Enterohepatic circulation of bile acids is fundamentally composed of two major processes, secretion from the liver and absorption from the intestine ( 30 /3A4 mice indicating increased canalicular membrane effl ux, and higher expression of Oatp2 and Ntcp mRNAs indicating increased hepatic bile acid uptake and effl ux. Therefore, lowered hepatic bile acid accumulation in Vdr ⌬ IEpC /3A4 mice might not be due to increased hepatic bile acid uptake leading to less bile acid accumulation, but due to lower enterohepatic bile acid circulation in these mice as a result of lower expression of Oatps , Asbt , and Ost ␣ .…”

Vitamin D and colon cancer

“…One of them is the drug efflux pump multi-drug resistance protein (MDR)-1, which is located in the enterocyte apical membrane (Pfrunder et al 2003, Aiba et al 2005). 1,25(OH) 2 D 3 also modulates the expression of members of the multi-drug resistanceassociated protein (MRP) family, which are involved in the transport of conjugated and unconjugated bile acids, and also in that of glutathione and sulphate conjugates (McCarthy et al 2005). …”