Biochimie et physiopathologie des nucléotides extracellulaires et des ectonucléotidases dans l'inflammation et le système digestif

 

Jean Sévigny

Centre de recherche du Centre hospitalier de l'Université Laval

 

Domaine : maladies infectieuses et immunitaires

Programme chercheurs nationaux

Concours 2014-2015

We now know that ATP can be released by all cells, either in a controlled or passive fashion. Interestingly, ATP is release in large amounts in inflammatory conditions. ATP is then perceived as a danger signal. A set of convincing data suggests that disordered ATP signaling contributes to the etiology of various diseases (e.g. inflammatory diseases and pain, cystic fibrosis, thrombosis, cancer).

Our laboratory seeks to elucidate the functions of ATP, which acts by the interaction with various receptors, and whose concentration is controlled by enzymes called ectonucleotidases. This complex system allows a tight regulation of the physiological responses activated by this ligand. We identified the receptors and the ectonucleotidases involved in such signaling in inflammatory functions. Moreover, we observed that a reduction in the activity of these ectonucleotidases favors thrombosis as well as increases the incidence of inflammatory bowel diseases.

We have obtained the support of the CIHR and of other organizations to determine the mechanisms involved in this new signaling pathway in inflammatory and infectious diseases. Over the last decade, we produced all the necessary tools to study these functions, of which a series of mutant mice which do not produce either a receptor or an ectonucleotidase involved in these functions.

We consider that a better knowledge of the mechanisms of ATP signaling will enable the targeting of new therapeutic pathways, which could be used to treat certain inflammatory such as hepatic fibrosis, arthritis, inflammatory bowel diseases, as well as infectious diseases.