Chromogranin A regulates gut permeability via the antagonistic actions of its proteolytic peptides.
Catestatin
chromogranin A
enteroendocrine cells
epithelial tight junctions
gut barrier
inflammatory bowel disease
Journal
Acta physiologica (Oxford, England)
ISSN: 1748-1716
Titre abrégé: Acta Physiol (Oxf)
Pays: England
ID NLM: 101262545
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
revised:
23
03
2021
received:
30
11
2020
accepted:
25
03
2021
pubmed:
31
3
2021
medline:
19
8
2021
entrez:
30
3
2021
Statut:
ppublish
Résumé
A "leaky" gut barrier has been implicated in the initiation and progression of a multitude of diseases, for example, inflammatory bowel disease (IBD), irritable bowel syndrome and celiac disease. Here we show how pro-hormone Chromogranin A (CgA), produced by the enteroendocrine cells, and Catestatin (CST: hCgA Colon tissues from region-specific CST-knockout (CST-KO) mice, CgA-knockout (CgA-KO) and WT mice were analysed by immunohistochemistry, western blot, ultrastructural and flowcytometry studies. FITC-dextran assays were used to measure intestinal barrier function. Mice were supplemented with CST or CgA fragment pancreastatin (PST: CgA Plasma levels of CST were elevated in IBD patients. CST-KO mice displayed (a) elongated tight, adherens junctions and desmosomes similar to IBD patients, (b) elevated expression of Claudin 2, and (c) gut inflammation. Plasma FITC-dextran measurements showed increased intestinal paracellular permeability in the CST-KO mice. This correlated with a higher ratio of Firmicutes to Bacteroidetes, a dysbiotic pattern commonly encountered in various diseases. Supplementation of CST-KO mice with recombinant CST restored paracellular permeability and reversed inflammation, whereas CgA-KO mice supplementation with CST and/or PST in CgA-KO mice showed that intestinal paracellular permeability is regulated by the antagonistic roles of these two peptides: CST reduces and PST increases permeability. The pro-hormone CgA regulates the intestinal paracellular permeability. CST is both necessary and sufficient to reduce permeability and primarily acts by antagonizing PST.
Identifiants
pubmed: 33783968
doi: 10.1111/apha.13655
pmc: PMC8341099
mid: NIHMS1724254
doi:
Substances chimiques
Chromogranin A
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13655Subventions
Organisme : BLRD VA
ID : I01 BX003934
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI141630
Pays : United States
Informations de copyright
© 2021 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
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