PIPE · Physiology of the Intestine: Proteases from the Epithelium

In several gastrointestinal diseases such as irritable bowel syndrome or inflammatory bowel diseases, proteolytic homeostasis is disrupted. This disruption has an important impact of the pathophysiology of those diseases. We hypothesized that intestinal epithelial cells are major regulators of this homeostasis by secreting proteases and protease inhibitors, thereby interfering with gut biological functions and enteric neuron biology.We have generated preliminary data demonstrating that stimulated intestinal epithelial cells release proteolytic activity predominantly on the basolateral side, suggesting that epithelium-derived proteases could then modify mucosal physiology and participate to the dialogue between epithelium and other mucosal cells such as enteric neurons.The aim of the project is to:1/ characterize the protease/anti-protease balance issued from intestinal epithelium,2/ study the impact of intestinal epithelium-derived proteolytic machinery on epithelial physiological functions3/ study the impact of intestinal epithelium-derived proteolytic factors on enteric nervous system activationWe believe that results raised from this study will identify previously unknown actors of intestine physiology and pathophysiology and of the neuro-epithelial crosstalks in the gut. Further, we believe that results generated from the present study could have implications more largely on our understanding of mucosal physiology.