INFLEMT · Functional role of Epithelial–to–Mesenchymal Transition in the pathogenesis of Inflammatory Bowel Disease

Functional role of Epithelial–to–Mesenchymal Transition in the pathogenesis of Inflammatory Bowel Disease

The INFLEMT project aims to address the functional role of the process termed Epithelial–to–Mesenchymal Transition (EMT) in the pathogenesis of Inflammatory Bowel Disease (IBD). IBD (with its two major manifestations: ulcerative colitis and Crohn’s disease) defines a group of chronic inflammatory disorders of the digestive tract representing a chronic idiopathic disease affecting 2.5 million people in Europe, with considerable costs for the health care system. Loss of work productivity and reduced quality of life are estimated to account for even higher costs than those associated with hospitalization, treatments and surgery. Compromised barrier functionality, chronic inflammation and persistent injury of the intestinal mucosa represent central drivers of IBD. This chronic tissue damage, with its recurring cycles of inflammation, remission and flare ups, triggers the development of intestinal fibrosis which is responsible for common IBD complications such as strictures and fistulae, all requiring surgical intervention. The global rise of IBD prevalence together with the challenges associated with the development of complications and the unresponsiveness to the new biological therapies are posing an urgent need to better understand the mechanisms underpinning IBD pathogenesis. The term EMT defines is a cellular trans-differentiation program by which epithelial cells lose their identity and acquire phenotypic and functional features typical of fibroblasts. EMT has been recently shown to represent an epithelial injury-induced damage response impairing cell functionality and regenerative capacity, and to be a fuel of fibrosis by modulating the immune response. The process of EMT has been implicated in the pathogenesis of IBD, but its precise functional role is currently unknown. The overall objective of the INFLEMT project was to determine the functional consequences the activation of the EMT program has in terms of epithelial injury response and modulation of inflammation and fibrogenic, pursuing the central hypothesis that EMT is a major functional driver in the pathogenesis of IBD. Specific objectives were the following: 1. Profile EMT in human IBD. 2. Elucidate the functional impact of EMT on the integrity and functionality of the intestinal epithelial barrier. 3. Explore the effects of EMT on the development of fibrosis and modulation of the immune cell response. The ultimate goal of INFLEMT was to provide a novel understanding of the epithelial-driven mechanisms supporting persistent damage and inflammation, which could allow to design innovative approaches to protect the intestinal mucosa in IBD patients. Since Europe has the highest global IBD prevalence, INFLEMT provides novel insights into the pathogenesis of a disease having a huge socio-economic impact in Europe.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз