Document Type
Article
Publication Title
Scientific Reports
Abstract
The breakdown of the intestinal barrier is a common manifestation of many diseases. Recent evidence suggests that vitamin D and its receptor VDR may regulate intestinal barrier function. Claudin-2 is a tight junction protein that mediates paracellular water transport in intestinal epithelia, rendering them "leaky". Using whole body VDR(-/-) mice, intestinal epithelial VDR conditional knockout (VDR(ΔIEC)) mice, and cultured human intestinal epithelial cells, we demonstrate here that the CLDN2 gene is a direct target of the transcription factor VDR. The Caudal-Related Homeobox (Cdx) protein family is a group of the transcription factor proteins which bind to DNA to regulate the expression of genes. Our data showed that VDR-enhances Claudin-2 promoter activity in a Cdx1 binding site-dependent manner. We further identify a functional vitamin D response element (VDRE) 5΄-AGATAACAAAGGTCA-3΄ in the Cdx1 site of the Claudin-2 promoter. It is a VDRE required for the regulation of Claudin-2 by vitamin D. Absence of VDR decreased Claudin-2 expression by abolishing VDR/promoter binding. In vivo, VDR deletion in intestinal epithelial cells led to significant decreased Claudin-2 in VDR(-/-) and VDR(ΔIEC) mice. The current study reveals an important and novel mechanism for VDR by regulation of epithelial barriers.
DOI
10.1038/srep10642
Publication Date
7-27-2015
ISSN
2045-2322
Recommended Citation
Zhang Y, Wu S, Lu R, Zhou D, Zhou J, Carmeliet G, Petrof E, Claud EC, Sun J. Tight Junction CLDN2 Gene is a Direct Target of the Vitamin D Receptor. Scientific Reports. 2015; 5. doi: 10.1038/srep10642.
