Lithocholic Acid Is a Vitamin D Receptor Ligand That Acts Preferentially in the Ileum
The vitamin D receptor (VDR) is a nuclear receptor that mediates the biological action of the active form of vitamin D, 1α,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃], and regulates calcium and bone metabolism. Lithocholic acid (LCA), which is a secondary bile acid produced by intestinal bacteria, acts as...
Gespeichert in:
Veröffentlicht in: | International journal of molecular sciences 2018-07, Vol.19 (7), p.1975 |
---|---|
Hauptverfasser: | , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | The vitamin D receptor (VDR) is a nuclear receptor that mediates the biological action of the active form of vitamin D, 1α,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃], and regulates calcium and bone metabolism. Lithocholic acid (LCA), which is a secondary bile acid produced by intestinal bacteria, acts as an additional physiological VDR ligand. Despite recent progress, however, the physiological function of the LCA−VDR axis remains unclear. In this study, in order to elucidate the differences in VDR action induced by 1,25(OH)₂D₃ and LCA, we compared their effect on the VDR target gene induction in the intestine of mice. While the oral administration of 1,25(OH)₂D₃ induced the
expression effectively in the duodenum and jejunum, the LCA increased target gene expression in the ileum as effectively as 1,25(OH)₂D₃. 1,25(OH)₂D₃, but not LCA, increased the expression of the calcium transporter gene
in the upper intestine, and increased the plasma calcium levels. Although LCA could induce an ileal
expression as well as 1,25(OH)₂D₃, the oral LCA administration was not effective in the VDR target gene induction in the kidney. No effect of LCA on the ileal
expression was observed in the VDR-null mice. Thus, the results indicate that LCA is a selective VDR ligand acting in the lower intestine, particularly the ileum. LCA may be a signaling molecule, which links intestinal bacteria and host VDR function. |
---|---|
ISSN: | 1422-0067 1661-6596 1422-0067 |
DOI: | 10.3390/ijms19071975 |