Cargando…
Vitamin D Receptor Upregulates Tight Junction Protein Claudin-5 against Colitis-Associated Tumorigenesis
Tight junctions are essential for barrier integrity, inflammation, and cancer. Vitamin D and the vitamin D receptor (VDR) play important roles in colorectal cancer (CRC). Using the human CRC database, we found colonic VDR expression was low and significantly correlated with a reduction of Claudin-5...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262815/ https://www.ncbi.nlm.nih.gov/pubmed/35338345 http://dx.doi.org/10.1038/s41385-022-00502-1 |
_version_ | 1784742585889193984 |
---|---|
author | Zhang, Yongguo Garrett, Shari Carroll, Robert E. Xia, Yinglin Sun, Jun |
author_facet | Zhang, Yongguo Garrett, Shari Carroll, Robert E. Xia, Yinglin Sun, Jun |
author_sort | Zhang, Yongguo |
collection | PubMed |
description | Tight junctions are essential for barrier integrity, inflammation, and cancer. Vitamin D and the vitamin D receptor (VDR) play important roles in colorectal cancer (CRC). Using the human CRC database, we found colonic VDR expression was low and significantly correlated with a reduction of Claudin-5 mRNA and protein. In the colon of VDR(ΔIEC) mice, deletion of intestinal VDR led to lower protein and mRNA levels of Claudin-5. Intestinal permeability was increased in the VDR(−/−) colon cancer model. Lacking VDR and a reduction of Claudin-5 are associated with an increased number of tumors in the VDR(−/−) and VDR(ΔIEC) mice. Furthermore, gain and loss functional studies have identified CLDN-5 as a downstream target of VDR. We identified the Vitamin D response element (VDRE) binding sites in a reporter system showed that VDRE in the Claudin-5 promoter is required for vitamin D(3)-induced Claudin-5 expression. Conditional epithelial VDR overexpression protected against the loss of Claudin-5 in response to inflammation and tumorigenesis in vivo. We also reported fecal VDR reduction in a colon cancer model. This study advances the understanding of how VDR regulates intestinal barrier functions in tumorigenesis and the possibility for identifying new biomarker and therapeutic targets to restore VDR-dependent functions in CRC. |
format | Online Article Text |
id | pubmed-9262815 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
record_format | MEDLINE/PubMed |
spelling | pubmed-92628152022-09-25 Vitamin D Receptor Upregulates Tight Junction Protein Claudin-5 against Colitis-Associated Tumorigenesis Zhang, Yongguo Garrett, Shari Carroll, Robert E. Xia, Yinglin Sun, Jun Mucosal Immunol Article Tight junctions are essential for barrier integrity, inflammation, and cancer. Vitamin D and the vitamin D receptor (VDR) play important roles in colorectal cancer (CRC). Using the human CRC database, we found colonic VDR expression was low and significantly correlated with a reduction of Claudin-5 mRNA and protein. In the colon of VDR(ΔIEC) mice, deletion of intestinal VDR led to lower protein and mRNA levels of Claudin-5. Intestinal permeability was increased in the VDR(−/−) colon cancer model. Lacking VDR and a reduction of Claudin-5 are associated with an increased number of tumors in the VDR(−/−) and VDR(ΔIEC) mice. Furthermore, gain and loss functional studies have identified CLDN-5 as a downstream target of VDR. We identified the Vitamin D response element (VDRE) binding sites in a reporter system showed that VDRE in the Claudin-5 promoter is required for vitamin D(3)-induced Claudin-5 expression. Conditional epithelial VDR overexpression protected against the loss of Claudin-5 in response to inflammation and tumorigenesis in vivo. We also reported fecal VDR reduction in a colon cancer model. This study advances the understanding of how VDR regulates intestinal barrier functions in tumorigenesis and the possibility for identifying new biomarker and therapeutic targets to restore VDR-dependent functions in CRC. 2022-04 2022-03-25 /pmc/articles/PMC9262815/ /pubmed/35338345 http://dx.doi.org/10.1038/s41385-022-00502-1 Text en http://www.nature.com/authors/editorial_policies/license.html#termsUsers may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Zhang, Yongguo Garrett, Shari Carroll, Robert E. Xia, Yinglin Sun, Jun Vitamin D Receptor Upregulates Tight Junction Protein Claudin-5 against Colitis-Associated Tumorigenesis |
title | Vitamin D Receptor Upregulates Tight Junction Protein Claudin-5 against Colitis-Associated Tumorigenesis |
title_full | Vitamin D Receptor Upregulates Tight Junction Protein Claudin-5 against Colitis-Associated Tumorigenesis |
title_fullStr | Vitamin D Receptor Upregulates Tight Junction Protein Claudin-5 against Colitis-Associated Tumorigenesis |
title_full_unstemmed | Vitamin D Receptor Upregulates Tight Junction Protein Claudin-5 against Colitis-Associated Tumorigenesis |
title_short | Vitamin D Receptor Upregulates Tight Junction Protein Claudin-5 against Colitis-Associated Tumorigenesis |
title_sort | vitamin d receptor upregulates tight junction protein claudin-5 against colitis-associated tumorigenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262815/ https://www.ncbi.nlm.nih.gov/pubmed/35338345 http://dx.doi.org/10.1038/s41385-022-00502-1 |
work_keys_str_mv | AT zhangyongguo vitamindreceptorupregulatestightjunctionproteinclaudin5againstcolitisassociatedtumorigenesis AT garrettshari vitamindreceptorupregulatestightjunctionproteinclaudin5againstcolitisassociatedtumorigenesis AT carrollroberte vitamindreceptorupregulatestightjunctionproteinclaudin5againstcolitisassociatedtumorigenesis AT xiayinglin vitamindreceptorupregulatestightjunctionproteinclaudin5againstcolitisassociatedtumorigenesis AT sunjun vitamindreceptorupregulatestightjunctionproteinclaudin5againstcolitisassociatedtumorigenesis |