| First Author | Zhang YG | Year | 2015 |
| Journal | Sci Rep | Volume | 5 |
| Pages | 10642 | PubMed ID | 26212084 |
| Mgi Jnum | J:250202 | Mgi Id | MGI:6102120 |
| Doi | 10.1038/srep10642 | Citation | Zhang YG, et al. (2015) Tight junction CLDN2 gene is a direct target of the vitamin D receptor. Sci Rep 5:10642 |
| abstractText | 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(DeltaIEC)) 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(DeltaIEC) mice. The current study reveals an important and novel mechanism for VDR by regulation of epithelial barriers. |
