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


Journal

Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440

Informations de publication

Date de publication:
19 Nov 2021
Historique:
entrez: 17 11 2021
pubmed: 18 11 2021
medline: 18 11 2021
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 34788088
doi: 10.1126/sciadv.abj6895
pmc: PMC8597994
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

eabj6895

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Auteurs

Yukako Oda (Y)

Department of Biosystems Science, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.

Chisato Takahashi (C)

Department of Molecular and Cellular BioAnalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
Laboratory of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kyoto 610-0395, Japan.

Shota Harada (S)

Laboratory of Human Interface, Graduate School of Systems Life Sciences, Kyushu University, Fukuoka 819-0395, Japan.

Shun Nakamura (S)

Cellular and Structural Physiology Laboratory, Advanced Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
CeSPIA Inc., Tokyo 100-0004, Japan.

Daxiao Sun (D)

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden 01309, Germany.

Kazumi Kiso (K)

Department of Biosystems Science, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.

Yuko Urata (Y)

Department of Biosystems Science, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.

Hitoshi Miyachi (H)

Reproductive Engineering Team, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.

Yoshinori Fujiyoshi (Y)

Cellular and Structural Physiology Laboratory, Advanced Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
CeSPIA Inc., Tokyo 100-0004, Japan.

Alf Honigmann (A)

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden 01309, Germany.

Seiichi Uchida (S)

Laboratory of Human Interface, Graduate School of Systems Life Sciences, Kyushu University, Fukuoka 819-0395, Japan.

Yasushi Ishihama (Y)

Department of Molecular and Cellular BioAnalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.

Fumiko Toyoshima (F)

Department of Biosystems Science, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.

Classifications MeSH