Differential Regulation of TauT by Calcitriol and Retinoic Acid via VDR/RXR in LLC-PK1 and MCF-7 Cells

Abstract

The interaction between taurine and the absorption of fat-soluble -vitamins, such as vitamin A and D, has been an interesting topic in the field of -nutrition science, because taurine-conjugated bile acid optimizes fat and fat-soluble vitamin absorption. However, whether the hormone calcitriol (1,25-dihydroxyvitamin D(3)) and retinoic acid regulate the expression of the TauT gene is unknown. In this study, we test the hypothesis that the TauT gene is regulated by vitamin D(3) (VD(3)) and retinoic acid (RA) via activation of the vitamin D receptor (VDR) and retinoic acid receptor (RXR). Taurine uptake, Western blotting, gene reporter assay, and immunohistochemical analysis of TauT, VDR, and RXR were used in VD(3)- and/or RA-treated LLC-PK1 and MCF-7 cells. We demonstrated that VD(3) alone had little effect on TauT expression in both LLC-PK1 and MCF-7 cells. Expression of TauT was significantly increased by RA, which was synergized by the addition of VD(3) after RXR activation in LLC-PK1 cells. In contrast, expression of TauT was significantly decreased by the combination of VD(3) and RA in MCF-7 cells. Regulation of TauT by VD(3)/RA appears to occur at the transcriptional level, as determined by a reporter gene assay of the TauT promoter. Immunohistochemical study showed that VDR and RXR were activated by VD(3) and RA, respectively, in both LLC-PK1 and MCF-7 cells. The activated VDR and RXR also colocated in nuclei of both cells, suggesting that a VDR/RXR complex is involved in the transcriptional regulation of TauT. Our results show that expression of TauT is differentially regulated by VD(3) and RA via formation of VDR and RXR complexes in the nuclei in a cell type-dependent manner.