Vitamin D Receptor Mediates Attenuating Effect of Lithocholic Acid on Dextran Sulfate Sodium Induced Colitis in Mice.
Hitomi KubotaMichiyasu IshizawaMakoto KodamaYoshihiro NagaseShigeaki KatoMakoto MakishimaKenichi SakuraiPublished in: International journal of molecular sciences (2023)
Bile acids are major components of bile; they emulsify dietary lipids for efficient digestion and absorption and act as signaling molecules that activate nuclear and membrane receptors. The vitamin D receptor (VDR) is a receptor for the active form of vitamin D and lithocholic acid (LCA), a secondary bile acid produced by the intestinal microflora. Unlike other bile acids that enter the enterohepatic circulation, LCA is poorly absorbed in the intestine. Although vitamin D signaling regulates various physiological functions, including calcium metabolism and inflammation/immunity, LCA signaling remains largely unknown. In this study, we investigated the effect of the oral administration of LCA on colitis in a mouse model using dextran sulfate sodium (DSS). Oral LCA decreased the disease activity of colitis in the early phase, which is a phenotype associated with the suppression of histological injury, such as inflammatory cell infiltration and goblet cell loss. These protective effects of LCA were abolished in VDR-deleted mice. LCA decreased the expression of inflammatory cytokine genes, but this effect was at least partly observed in VDR-deleted mice. The pharmacological effect of LCA on colitis was not associated with hypercalcemia, an adverse effect induced by vitamin D compounds. Therefore, LCA suppresses DSS-induced intestinal injury in its action as a VDR ligand.
Keyphrases
- disease activity
- mouse model
- oxidative stress
- rheumatoid arthritis
- systemic lupus erythematosus
- single cell
- high fat diet induced
- poor prognosis
- rheumatoid arthritis patients
- ankylosing spondylitis
- stem cells
- genome wide
- adipose tissue
- metabolic syndrome
- type diabetes
- mesenchymal stem cells
- transcription factor
- gene expression
- diabetic rats
- juvenile idiopathic arthritis
- high resolution
- electronic health record
- anaerobic digestion
- insulin resistance
- adverse drug