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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 21, 2016; 22(11): 3117-3126
Published online Mar 21, 2016. doi: 10.3748/wjg.v22.i11.3117
Tight junctions in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer
Jonathan Landy, Emma Ronde, Nick English, Sue K Clark, Ailsa L Hart, Stella C Knight, Paul J Ciclitira, Hafid Omar Al-Hassi
Jonathan Landy, Ailsa L Hart, IBD Unit, St Mark’s Hospital, Harrow, London HA1 3UJ, United Kingdom
Jonathan Landy, Emma Ronde, Nick English, Ailsa L Hart, Stella C Knight, Hafid Omar Al-Hassi, Antigen Presentation Research Group, Department of Immunology, Imperial College, London HA1 3UJ, United Kingdom
Sue K Clark, Department of Biosurgery and Surgical Technology, Imperial College, London HA1 3UJ, United Kingdom
Paul J Ciclitira, Department of Gastroenterology, The Rayne Institute, St Thomas’ Hospital, London HA1 3UJ, United Kingdom
Author contributions: Landy J and Al-Hassi HO contributed equally to the conception of the article, literature search and interpretation, writing the article and making critical revisions related to important intellectual content of the manuscript, and final approval of the version of the article to be published; Ronde E contributed to the literature search, drafting of the article and final approval of the version of the article to be published; English N was responsible for the electron micrographs presented in the figures; Clark SK, Knight SC, Hart AL and Ciclitira PJ made critical revisions related to important intellectual content of the manuscript, and the final approval of the version of the article to be published.
Supported by The Association for International Cancer Research (AICR, to Dr. Al-Hassi HO), Scotland; Funded by the AICR, grant No. 120234; a BBSRC Strategic Research Grant (to English N and Knight SC; WMNIP33458); the St Mark’s Hospital Foundation, United Kingdom.
Conflict-of-interest statement: None of the authors have any conflicts of interest or financial disclosures; and Dr. Hart has spoken for and is on the advisory board for MSD, Shire and Abbott.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Paul J Ciclitira, Professor, Department of Gastroenterology, The Rayne Institute, St Thomas’ Hospital, 4th Floor Lambeth Wing, London SE1 7EH, United Kingdom. paul.ciclitira@kcl.ac.uk
Telephone: +44-20-76202597 Fax: +44-20-72610667
Received: June 18, 2015
Peer-review started: June 21, 2015
First decision: August 26, 2015
Revised: September 19, 2015
Accepted: December 19, 2015
Article in press: December 19, 2015
Published online: March 21, 2016
Processing time: 270 Days and 8.7 Hours
Abstract

Inflammatory bowel diseases are characterised by inflammation that compromises the integrity of the epithelial barrier. The intestinal epithelium is not only a static barrier but has evolved complex mechanisms to control and regulate bacterial interactions with the mucosal surface. Apical tight junction proteins are critical in the maintenance of epithelial barrier function and control of paracellular permeability. The characterisation of alterations in tight junction proteins as key players in epithelial barrier function in inflammatory bowel diseases is rapidly enhancing our understanding of critical mechanisms in disease pathogenesis as well as novel therapeutic opportunities. Here we give an overview of recent literature focusing on the role of tight junction proteins, in particular claudins, in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer.

Keywords: Claudin; Tight junction; Ulcerative colitis; Pouchitis; Crohn’s disease

Core tip: Epithelial barrier function is compromised in inflammatory bowel diseases (IBD). Apical tight junction proteins, in particular claudins, are key players in epithelial barrier function. However, there is little consensus regarding the expression of most claudin isoforms in these conditions or whether these findings are primary or secondary to disease pathogenesis. Knowledge of tight junction protein expression and function in IBD and IBD associated colorectal cancer will enhance our understanding of critical mechanisms in disease pathogenesis as well as novel therapeutic opportunities.