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World J Gastroenterol. Jun 7, 2020; 26(21): 2702-2714
Published online Jun 7, 2020. doi: 10.3748/wjg.v26.i21.2702
Role of regenerating islet-derived proteins in inflammatory bowel disease
Jodi-Ann Edwards, Nicholas Tan, Nadlie Toussaint, Peiqi Ou, Cathy Mueller, Albert Stanek, Vladimir Zinsou, Sean Roudnitsky, Michelle Sagal, Lisa Dresner, Alexander Schwartzman, Chongmin Huan
Jodi-Ann Edwards, Cathy Mueller, Albert Stanek, Sean Roudnitsky, Michelle Sagal, Lisa Dresner, Alexander Schwartzman, Department of Surgery, State University of New York, Downstate Health Sciences University, Brooklyn, NY 11203, United States
Nicholas Tan, Nadlie Toussaint, Vladimir Zinsou, College of Medicine, State University of New York, Downstate Health Sciences University, Brooklyn, NY 11203, United States
Peiqi Ou, MCB program, School of Graduate Studies, State University of New York, Downstate Health Sciences University, Brooklyn, NY 11203, United States
Chongmin Huan, Department of Surgery and Cell Biology, State University of New York, Downstate Health Sciences University, Brooklyn, NY 11203, United States
Author contributions: Edwards JA, Tan N, Toussaint N and Huan C conceptualized, designed and drafted the manuscript; Edwards JA, Tan N, Toussaint N, Ou P, Mueller C, Stanek A, Zinsou V, Roudnitsky S, Sagal M and Huan C reviewed the literatures; Edwards JA, Toussaint N, Ou P, Mueller C, Stanek A, Dresner L, Schwartzman A and Huan C discussed and edited the manuscript; Huan C directed the study.
Conflict-of-interest statement: There is no conflict of interest associated with the senior author or other coauthors contributed their efforts in this manuscript.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/
Corresponding author: Chongmin Huan, MD, PhD, Assistant Professor, Department of Surgery and Cell Biology, State University of New York, Downstate Health Sciences University, 450 Clarkson Ave, Brooklyn, NY 11203, United States. chongmin.huan@downstate.edu
Received: January 21, 2020
Peer-review started: January 21, 2020
First decision: March 15, 2020
Revised: March 26, 2020
Accepted: May 13, 2020
Article in press: May 13, 2020
Published online: June 7, 2020
Processing time: 136 Days and 19.5 Hours
Abstract

Inflammatory bowel disease (IBD) is an inflammatory disorder of the gastrointestinal tract that affects millions of patients worldwide. It has a complex and multifactorial etiology leading to excessive exposure of intestinal epithelium to microbial antigens, inappropriate activation of the immune system and ultimately to the damage of intestinal tissues. Although numerous efforts have been made to improve the disease management, IBD remains persistently recurring and beyond cure. This is due largely to the gaps in our understanding of the pathogenesis of IBD that hamper the development of timely diagnoses and effective treatment. However, some recent discoveries, including the beneficial effects of interleukin-22 (IL-22) on the inflamed intestine, have shed light on a self-protective mechanism in IBD. Regenerating islet-derived (REG/Reg) proteins are small secretory proteins which function as IL-22’s downstream effectors. Mounting studies have demonstrated that IBD patients have significantly increased REG expressions in the injured intestine, but with undefined mechanisms and roles. The reported functions of REG/Reg proteins in intestinal homeostasis, such as those of antibacterial, anti-inflammatory and tissue repair, lead us to discuss their potential mechanisms and clinical relevance in IBD in order to advance IBD research and management.

Keywords: Regenerating islet-derived proteins; Inflammatory bowel disease; Crohn’s disease; Ulcerative colitis; Interleukin-22; Intestinal bacteria

Core tip: The clinical management of inflammatory bowel disease (IBD) remains a significant challenge due to the knowledge gap in its pathogenesis. In this review paper, we have discussed the literature regarding increased expressions of regenerating islet-derived proteins in IBD and proposed the potential clinical relevance of these proteins based on their known protective activities in the inflamed intestine. We therefore provide insight from a new perspective in order to advance IBD research and clinical management.