title: Visceral hypersensitivity in inflammatory bowel diseases and irritable bowel syndrome: The role of proteases.
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.
authors.affiliation: 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.
authors.forename: Hannah
authors.initials: H
authors.lastname: Ceuleers
authors.affiliation: 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.
authors.forename: Hanne
authors.initials: H
authors.lastname: Van Spaendonk
authors.affiliation: 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.
authors.forename: Nikita
authors.initials: N
authors.lastname: Hanning
authors.affiliation: 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.
authors.forename: Jelena
authors.initials: J
authors.lastname: Heirbaut
authors.affiliation: 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.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Lambeir
authors.affiliation: 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.
authors.forename: Jurgen
authors.initials: J
authors.lastname: Joossens
authors.affiliation: 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.
authors.forename: Koen
authors.initials: K
authors.lastname: Augustyns
authors.affiliation: 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.
authors.forename: Joris G
authors.initials: JG
authors.lastname: De Man
authors.affiliation: 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.
authors.forename: Ingrid
authors.initials: I
authors.lastname: De Meester
authors.affiliation: 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.
authors.forename: Benedicte Y
authors.initials: BY
authors.lastname: De Winter
mesh_terms: D015746:Abdominal Pain / Q000188:drug therapy / Q000201:enzymology / Q000209:etiology* / Q000503:physiopathology; D000818:Animals; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy / Q000201:enzymology / Q000209:etiology* / Q000503:physiopathology; D015212:Inflammatory Bowel Diseases / Q000150:complications* / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D007408:Intestinal Absorption; D007422:Intestines / Q000201:enzymology* / Q000294:innervation; D043183:Irritable Bowel Syndrome / Q000150:complications* / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D010447:Peptide Hydrolases / Q000378:metabolism*; D010539:Permeability; D011480:Protease Inhibitors / Q000627:therapeutic use; D044462:Receptors, Proteinase-Activated / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D011480:Protease Inhibitors; D044462:Receptors, Proteinase-Activated; D010447:Peptide Hydrolases
keywords: Inflammatory bowel diseases; Irritable bowel syndrome; Protease inhibitors; Proteases; Proteinase-activated receptors; Visceral hypersensitivity; Visceral pain