title: 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.affiliation: Department of Medicine, Division of Biological Sciences, The University of Chicago, Chicago, IL 60637, USA. Electronic address: cyan@medicine.bsd.uchicago.edu.
authors.forename: Yan Chun
authors.initials: YC
authors.lastname: Li
authors.affiliation: Department of Medicine, Division of Biological Sciences, The University of Chicago, Chicago, IL 60637, USA; Laboratory of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, Liaoning 110001, China.
authors.forename: Yunzi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Laboratory of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, Liaoning 110001, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Du
mesh_terms: D000818:Animals; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D041981:Gastrointestinal Tract / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015212:Inflammatory Bowel Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000473:pathology; D018167:Receptors, Calcitriol / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D018167:Receptors, Calcitriol
keywords: Colitis; Inflammatory bowel diseases; Intestinal epithelial cells; MiR-346; Mucosal barrier; Mucosal inflammation; TNF-alpha; Vitamin D receptor