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Discovery of anti-inflammatory physiological peptides that promote tissue repair by reinforcing epithelial barrier formation.


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.

SUBMITTER: Oda Y 

PROVIDER: S-EPMC8597994 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Discovery of anti-inflammatory physiological peptides that promote tissue repair by reinforcing epithelial barrier formation.

Oda Yukako Y   Takahashi Chisato C   Harada Shota S   Nakamura Shun S   Sun Daxiao D   Kiso Kazumi K   Urata Yuko Y   Miyachi Hitoshi H   Fujiyoshi Yoshinori Y   Honigmann Alf A   Uchida Seiichi S   Ishihama Yasushi Y   Toyoshima Fumiko F  

Science advances 20211117 47


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-antitr  ...[more]

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