Targeting AMPK for the Control of Intestinal epithelial barrier integrity – TACI

Rupture of intestinal epithelial barrier (IEB) integrity is associated with a variety of gastrointestinal disorders. In particular IEB permeability is increased in inflammatory bowel disease or obesity and strengthening of the IEB has been associated with better clinical outcomes. Our preliminary data has identified AMP-activated protein kinase (AMPK) as an epithelial target of permeability regulation, but data regarding its role in IEB integrity remain sparse. The overall objective of this project is to study the role of AMPK in the maintenance of IEB homeostasis. The specific aims are 1) to explore the impact of AMPK dysregulation on IEB rupture and development inflammation; 2) to validate strategies of IEB strengthening or restoration by activation of AMPK. Our project will combine molecular and functional analyzes of human pathological/control samples to examination of mice model developing low or high grade chronic inflammation with or without AMPK activation in epithelial cells.