Critical roles of intestinal epithelial vitamin D receptor signaling in controlling gut mucosal inflammation.

Abstract

Although vitamin D receptor (VDR) is highly expressed in the intestine, the role of VDR signaling in the gut is not fully understood. Our recent studies unveil a regulatory circuit that centers gut epithelial VDR as a key molecule in the control of mucosal inflammation and colitis development. On the one hand, intestinal epithelial VDR signaling protects the integrity of the mucosal barrier by inhibiting inflammation-induced epithelial cell apoptosis. This barrier-protecting, anti-colitic activity is independent of the non-epithelial immune VDR actions. A healthy and intact mucosal barrier prevents bacterial invasion and thus reduces mucosal inflammation. On the other hand, inflammation in turn down-regulates epithelial VDR expression by inducing VDR-targeting microRNA-346, thus compromising mucosal barrier functions. Consistently, colonic epithelial VDR levels are markedly reduced in patients with inflammatory bowel diseases or in experimental colitis models, whereas vitamin D analog therapy that ameliorates colitis up-regulates epithelial VDR. Thus, gut epithelial VDR signaling appears to play an essential role in controlling mucosal inflammation and thus could be a useful therapeutic target in the management of inflammatory bowel diseases. This article is part of a special issue entitled '17th Vitamin D Workshop' .

• Authors: Yan Chun Li, Yunzi Chen, Jie Du
• Journal: The Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 148 Pg. 179-83 (Apr 2015) ISSN: 1879-1220 [Electronic] England
• PMID: 25603468 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Receptors, Calcitriol

Topics

• Animals
• Epithelial Cells (metabolism, pathology)
• Gastrointestinal Tract (metabolism, pathology)
• Humans
• Inflammation (metabolism, pathology, prevention & control)
• Inflammatory Bowel Diseases (metabolism, pathology, prevention & control)
• Intestinal Mucosa (metabolism)
• Intestines (pathology)
• Receptors, Calcitriol (agonists, metabolism)
• Signal Transduction