Discovery of tight junction inducing peptides that promote epithelial tissue repair in mammals

 

Yukako Oda

iPS cell Research Institute, Kyoto University, Kyoto, Japan

 

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 that corresponded to 35–42 residue peptides of the C-terminus of alpha 1-antitrypsin (A1AT), an acute phase anti-inflammatory protein abundant in circulating blood. 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 (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.

 

 

References

1.Oda Y, Takahashi C, Harada S, Nakamura S, Sun D, Kiso K, Urata Y, Miyachi H, Fujiyoshi Y, Honigmann A, Uchida S, Ishihama Y, Toyoshima FDiscovery of anti-inflammatory physiological peptides that promote tissue repair by reinforcing epithelial barrier formation

Science Advances, 7(47) eabj6895 (2021)

 

2. 小田裕香子

上皮組織の修復を促進する新規生体由来ペプチドJIPの発見

医学のあゆみ, 283 (4), 286-287 (2022)

 

3.小田裕香子

タイトジャンクションの形成を誘導する新規生理活性ペプチドJIPの発見

日本生化学会会誌「生化学」ミニレビュー, 94 (5), 715-719 (2022)