| First Author | Oda Y | Year | 2021 |
| Journal | Sci Adv | Volume | 7 |
| Issue | 47 | Pages | eabj6895 |
| PubMed ID | 34788088 | Mgi Jnum | J:327882 |
| Mgi Id | MGI:6842185 | Doi | 10.1126/sciadv.abj6895 |
| Citation | Oda Y, et al. (2021) Discovery of anti-inflammatory physiological peptides that promote tissue repair by reinforcing epithelial barrier formation. Sci Adv 7(47):eabj6895 |
| abstractText | Epithelial barriers that prevent dehydration and pathogen invasion are established by tight junctions (TJs), 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 found TJ-inducing peptides (JIPs) in mice and humans that corresponded to 35 to 42 residue peptides of the C terminus of alpha 1-antitrypsin (A1AT), an acute-phase anti-inflammatory protein. JIPs were inserted into the plasma membrane of epithelial cells, which promoted TJ formation by directly activating the heterotrimeric G protein G13. In a mouse intestinal epithelial injury model established by dextran sodium sulfate, mouse or human JIP 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 previously unidentified therapeutic strategy for TJ-disrupted diseases. |
