Role of Proteases and Protease-activated Receptor 2 in the Regulation of Physiological Colonic Barrier Function and in the Pathogenesis of Visceral Hypersensitivity
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Protease activated receptor 2: a new target for IBS treatment.
Proteinase-activated receptors (PARs) are G-protein-coupled receptors that are activated by the proteolytic cleavage of their N-terminal domain. The new N-terminal sequence that is exposed by proteolysis acts as a tethered ligand, which binds to and activates the receptor. PAR-2 is highly expressed in the gastrointestinal tract, where it is found in endothelial cells, colonic myocytes, enterocy...
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Colonic brain-derived neurotrophic factor (BDNF) plays an essential role in pathogenesis of abdominal pain in diarrhea-predominant irritable bowel syndrome (IBS-D), but regulation on its expression remains unclear. We investigated the role of fecal supernatants (FSN) from IBS-D patients on regulating BDNF expression in colonic epithelial cells of human and mice. Using human Caco-2 cells, we fou...
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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, ...
متن کاملRole for protease activity in visceral pain in irritable bowel syndrome.
Mediators involved in the generation of symptoms in patients with irritable bowel syndrome (IBS) are poorly understood. Here we show that colonic biopsy samples from IBS patients release increased levels of proteolytic activity (arginine cleavage) compared to asymptomatic controls. This was dependent on the activation of NF-kappaB. In addition, increased proteolytic activity was measured in viv...
متن کاملCathepsin S is activated during colitis and causes visceral hyperalgesia by a PAR2-dependent mechanism in mice.
BACKGROUND & AIMS Although proteases control inflammation and pain, the identity, cellular origin, mechanism of action, and causative role of proteases that are activated during disease are not defined. We investigated the activation and function of cysteine cathepsins (Cat) in colitis. METHODS Because protease activity, rather than expression, is regulated, we treated mice with fluorescent a...
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تاریخ انتشار 2011