Published online Dec 21, 2016. doi: 10.3748/wjg.v22.i47.10275
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
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.
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.