[Women and Future in Science Seminar]Discovery of mammalian tissue-derived peptides that promote tissue-repair by inducing tight junction formation
Nov. 29, 2021 15:00 - 15:30
Advance registration is required for participants outiside of RIKEN BDR.
Tight junctions (TJs) are epithelial barriers that prevent dehydration and pathogen invasion, and their disruption leads to various inflammatory diseases and tissue destruction. However, a therapeutic strategy to overcome TJ disruption in diseases has not been established because of the lack of clinically applicable TJ-inducing molecules. Here, we discovered TJ-inducing peptides (JIPs) in mice and humans, which corresponded to 35–40 residue peptides of the C-terminus of alpha 1-antitrypsin (A1AT), an acute phase anti-inflammatory protein abundant in circulating blood. JIPs inserted into the plasma membrane of epithelial cells, which induced TJs by directly activating the heterotrimeric G protein G13. In a mouse intestinal epithelial injury model established by dextran sodium sulfate (DSS), inhibition of JIPs impeded the restoration of TJs in regenerating intestinal epithelial cells, whereas mouse or human JIPs administration restored TJ integrity and strongly prevented colitis. Our study has revealed TJ-inducing anti- inflammatory physiological peptides that play a critical role in tissue repair and proposes a novel therapeutic strategy for TJ- disrupted diseases.
BDR Diversity Working Group