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Physiology of the Intestine: Proteases from the Epithelium

Objectif

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 functions
3/ study the impact of intestinal epithelium-derived proteolytic factors on enteric nervous system activation
We 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.

Appel à propositions

ERC-2012-StG_20111109
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Régime de financement

ERC-SG - ERC Starting Grant

Institution d’accueil

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Contribution de l’UE
€ 1 287 000,00
Adresse
RUE DE TOLBIAC 101
75654 Paris
France

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Région
Ile-de-France Ile-de-France Paris
Type d’activité
Research Organisations
Chercheur principal
Nathalie Vergnolle (Dr.)
Contact administratif
Muriel Bouas (Mrs.)
Liens
Coût total
Aucune donnée

Bénéficiaires (1)