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

J Steroid Biochem Mol Biol. 2015 Apr;148:179-83. doi: 10.1016/j.jsbmb.2015.01.011. Epub 2015 Jan 17.

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' .

Keywords: Colitis; Inflammatory bowel diseases; Intestinal epithelial cells; MiR-346; Mucosal barrier; Mucosal inflammation; TNF-alpha; Vitamin D receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

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

Substances

  • Receptors, Calcitriol