Discovery of anti-inflammatory physiological peptides that promote tissue repair by reinforcing epithelial barrier formation
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
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.
Details
Original language | English |
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Pages (from-to) | eabj6895 |
Journal | Science advances |
Volume | 7 |
Issue number | 47 |
Publication status | Published - 19 Nov 2021 |
Peer-reviewed | Yes |
External IDs
PubMedCentral | PMC8597994 |
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Scopus | 85119362864 |
ORCID | /0000-0003-0475-3790/work/155291290 |