Review
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2016; 22(47): 10275-10286
Published online Dec 21, 2016. doi: 10.3748/wjg.v22.i47.10275
Visceral hypersensitivity in inflammatory bowel diseases and irritable bowel syndrome: The role of proteases
Hannah Ceuleers, Hanne Van Spaendonk, Nikita Hanning, Jelena Heirbaut, Anne-Marie Lambeir, Jurgen Joossens, Koen Augustyns, Joris G De Man, Ingrid De Meester, Benedicte Y De Winter
Hannah Ceuleers, Hanne Van Spaendonk, Nikita Hanning, Jelena Heirbaut, Joris G De Man, Benedicte Y De Winter, Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, 2610 Antwerp, Belgium
Anne-Marie Lambeir, Ingrid De Meester, Laboratory of Medical Biochemistry, University of Antwerp, 2610 Antwerp, Belgium
Jurgen Joossens, Koen Augustyns, Laboratory of Medicinal Chemistry and Antwerp Drug Discovery Network, University of Antwerp, 2610 Antwerp, Belgium
Author contributions: All authors contributed equally to this paper with conception and design of the study, literature review and analysis, drafting and critical review and editing and approval of the final version.
Supported by University Research Fund Doctoral Projects (BOF-DOCPRO), No. DOCPRO4 2014/ID 2964; and Research Foundation Flanders (FWO), No. G034113N.
Conflict-of-interest statement: No potential conflicts of interest.
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: Benedicte Y De Winter, Professor, MD, PhD, Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Universiteitsplein 1, 2610 Antwerpen, Belgium. benedicte.dewinter@uantwerpen.be
Telephone: +32-3-2652710 Fax: +32-3-2652567
Received: September 21, 2016
Peer-review started: September 22, 2016
First decision: October 20, 2016
Revised: November 10, 2016
Accepted: December 2, 2016
Article in press: December 2, 2016
Published online: December 21, 2016
Abstract

Proteases, enzymes catalyzing the hydrolysis of peptide bonds, are present at high concentrations in the gastrointestinal tract. Besides their well-known role in the digestive process, they also function as signaling molecules through the activation of protease-activated receptors (PARs). Based on their chemical mechanism for catalysis, proteases can be classified into several classes: serine, cysteine, aspartic, metallo- and threonine proteases represent the mammalian protease families. In particular, the class of serine proteases will play a significant role in this review. In the last decades, proteases have been suggested to play a key role in the pathogenesis of visceral hypersensitivity, which is a major factor contributing to abdominal pain in patients with inflammatory bowel diseases and/or irritable bowel syndrome. So far, only a few preclinical animal studies have investigated the effect of protease inhibitors specifically on visceral sensitivity while their effect on inflammation is described in more detail. In our accompanying review we describe their effect on gastrointestinal permeability. On account of their promising results in the field of visceral hypersensitivity, further research is warranted. The aim of this review is to give an overview on the concept of visceral hypersensitivity as well as on the physiological and pathophysiological functions of proteases herein.

Keywords: Proteases, Proteinase-activated receptors, Protease inhibitors, Visceral hypersensitivity, Visceral pain, Irritable bowel syndrome, Inflammatory bowel diseases

Core tip: Proteases are enzymes catalyzing the hydrolysis of peptide bonds. They are present at high levels in the gastrointestinal tract and they execute a large variety of physiological and pathophysiological functions. In the last decade, it became clear that proteases fulfill an important role in visceral pain, a major symptom in patients with inflammatory bowel diseases and/or irritable bowel syndrome. These review articles aim at providing an overview of the diverse roles of proteases in both health and disease states related to the gastrointestinal functions, with the emphasis on visceral pain in this review.