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

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 t...

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Published in:Science advances 2021-11, Vol.7 (47), p.eabj6895-eabj6895
Main Authors: Oda, Yukako, Takahashi, Chisato, Harada, Shota, Nakamura, Shun, Sun, Daxiao, Kiso, Kazumi, Urata, Yuko, Miyachi, Hitoshi, Fujiyoshi, Yoshinori, Honigmann, Alf, Uchida, Seiichi, Ishihama, Yasushi, Toyoshima, Fumiko
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container_issue 47
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container_title Science advances
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creator Oda, Yukako
Takahashi, Chisato
Harada, Shota
Nakamura, Shun
Sun, Daxiao
Kiso, Kazumi
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Miyachi, Hitoshi
Fujiyoshi, Yoshinori
Honigmann, Alf
Uchida, Seiichi
Ishihama, Yasushi
Toyoshima, Fumiko
description 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.
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Cell Biology
Health and Medicine
SciAdv r-articles
title Discovery of anti-inflammatory physiological peptides that promote tissue repair by reinforcing epithelial barrier formation
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