Proteolytic bacteria expansion during colitis amplifies inflammation through cleavage of the external domain of PAR2.

ABSTRACT: Imbalances in proteolytic activity have been linked to the development of inflammatory bowel diseases (IBD) and experimental colitis. Proteases in the intestine play important roles in maintaining homeostasis, but exposure of mucosal tissues to excess proteolytic activity can promote pathology through protease-activated receptors (PARs). Previous research implicates microbial proteases in IBD, but the underlying pathways and specific interactions between microbes and PARs remain unclear. In this study, we investigated the role of microbial proteolytic activation of the external domain of PAR2 in intestinal injury using mice expressing PAR2 with a mutated N-terminal external domain that is resistant to canonical activation by proteolytic cleavage. Our findings demonstrate the key role of pr

SUBMITTER: Rondeau LE 

PROVIDER: S-EPMC11346554 | biostudies-literature | 2024 Jan-Dec

REPOSITORIES: biostudies-literature