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| 1 | Visceral hypersensitivity in inflammatory bowel diseases and irritable bowel syndrome: The role of proteases显示文摘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. | 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 | 2016 | World Journal of Gastroenterology2016，22，47： | 7 |
| 2 | Regulation of intestinal permeability: The role of proteases显示文摘The gastrointestinal barrier is-with approximately 400 m^2-the human body's largest surface separating the external environment from the internal milieu. This barrier serves a dual function: permitting the absorption of nutrients, water and electrolytes on the one hand, while limiting host contact with noxious luminal antigens on the other hand. To maintain this selective barrier, junction protein complexes seal the intercellular space between adjacent epithelial cells and regulate the paracellular transport. Increased intestinal permeability is associated with and suggested as a player in the pathophysiology of various gastrointestinal and extraintestinal diseases such as inflammatory bowel disease, celiac disease and type 1 diabetes. The gastrointestinal tract is exposed to high levels of endogenous and exogenous proteases, both in the lumen and in the mucosa. There is increasing evidence to suggest that a dysregulation of the protease/antiprotease balance in the gut contributes to epithelial damage and increased permeability. Excessive proteolysis leads to direct cleavage of intercellular junction proteins, or to opening of the junction proteins via activation of protease activated receptors. In addition, proteases regulate the activity and availability of cytokines and growth factors, which are also known modulators of intestinal permeability. This review aims at outlining the mechanisms by which proteases alter the intestinal permeability. More knowledge on the role of proteases in mucosal homeostasis and gastrointestinal barrier function will definitely contribute to the identification of new therapeutic targets for permeability-related diseases. | Hanne Van Spaendonk Hannah Ceuleers Leonie Witters Eveline Patteet Jurgen Joossens Koen Augustyns Anne-Marie Lambeir Ingrid De Meester Joris G De Man Benedicte Y De Winter | 2017 | World Journal of Gastroenterology2017，23，12： | 6 |
| 3 | Metabolism and toxicity of thioacetamide and thioacetamide S-oxide in rat hepatocytes 显示文摘 | Hajovsky H Hu G Koen Y | 2012 | Chem Res Toxicol2012，25，9： | 1 |
| 4 | The arterial wall: a new pharmacological and therapeutic target显示文摘 | Laurent S Vanhoutte P Cavero I Chabrier PE Dupuis B Elghozi JL Hamon G Janiak P Juillet Y Kher A Koen R Madonna O Maffrand JP Pruneau D Thuillez C | 1996 | Fundam Clin Pharmacol1996，10，3： | 1 |
| 5 | Clinical hurdles for the transplantation of cardiomyocytes derived from human embryonic stem cells: role of molecular imaging 显示文摘 | Swijnenburg R J Koen E A van der Bogt Sheikh A Y | 2007 | Current Opinion Bio2007，18，1： | 1 |
| 6 | Design and overall energy per-fonnance of a ventilated photovoltaic facade显示文摘 | Geun Y Y Mike M Koen S | 2007 | Solar Evergy2007，81，： | 1 |
| 7 | Design and overall energy performance of a ventilated photovoltaic facade 显示文摘 | Gem1 Y Y Mike M Koen S | 2007 | Solar Energy2007，81，： | 1 |
| 8 | Design and Overall Energy Perfor- naance of a Ventilated Photovoltaic Facade 显示文摘 | Geun Y Y Mike M Koen S | 2007 | Solar Energy2007，81，： | 1 |
| 9 | Energy policy and standard for built environment in China显示文摘 | Baizhan L Koen S | 2005 | Renewable Energy2005，30，13： | 1 |
| 10 | Fluidized bed upgrading of wood pyrolysis liquids and related compounds显示文摘 | CHEN N Y WALSH D E KOENING L R | | 0，，24： | 1 |
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