Cingulin is dispensable for epithelial barrier function and tight junction structure, and plays a role in the control of claudin-2 expression and response to duodenal mucosa injury.

Détails

ID Serval
serval:BIB_CAAFD777E00F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Cingulin is dispensable for epithelial barrier function and tight junction structure, and plays a role in the control of claudin-2 expression and response to duodenal mucosa injury.
Périodique
Journal of Cell Science
Auteur(s)
Guillemot L., Schneider Y., Brun P., Castagliuolo I., Pizzuti D., Martines D., Jond L., Bongiovanni M., Citi S.
ISSN
1477-9137 (Electronic)
ISSN-L
0021-9533
Statut éditorial
Publié
Date de publication
2012
Volume
125
Numéro
Pt 21
Pages
5005-5014
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Cingulin (CGN) is a 140 kDa protein, which is localized to the cytoplasmic region of vertebrate tight junctions (TJ), and regulates gene expression and RhoA signaling in cultured cells. To investigate the function of CGN at the organism level, we generated CGN knockout (CGN(-/-)) mice by homologous recombination. CGN(-/-) mice are viable and fertile, and are born at the expected mendelian ratios. Immunohistochemistry, immunofluorescence, electron microscopy and permeability assays of epithelial tissues of CGN(-/-) mice show no cingulin labeling at junctions, a normal localization of TJ proteins, and normal TJ structure and barrier function. Microarray analysis of intestinal cells does not show significant changes in gene expression between CGN(-/-) and CGN(+/+) mice, whereas immunoblotting analysis shows a twofold increase in the levels of claudin-2 protein in the duodenum and the kidney of CGN(-/-) mice, compared to CGN(+/+) littermates. Furthermore, CGN(-/-) mice show an exacerbated response to the ulcerogenic action of cysteamine, whereas acute injury of the colon by dextran sodium sulfate elicits undistinguishable responses in CGN(-/-) and CGN(+/+) mice. We conclude that at the organism level cingulin is dispensable for the structure and barrier function of TJ, and is embedded in signaling networks that control the expression of claudin-2, and the mucosal response to acute injury in the duodenum.
Mots-clé
Animals, Claudins/genetics, Claudins/metabolism, Cysteamine, Cytokines/blood, Dextran Sulfate/pharmacology, Duodenal Ulcer/chemically induced, Duodenal Ulcer/metabolism, Duodenum/metabolism, Duodenum/pathology, Gene Expression, Gene Knockout Techniques, Inflammation Mediators/blood, Intestinal Mucosa/metabolism, Intestinal Mucosa/pathology, Kidney/metabolism, Kidney/pathology, Liver/metabolism, Membrane Proteins/genetics, Membrane Proteins/metabolism, Mice, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Knockout, Organ Specificity, Permeability, Tight Junction Proteins/genetics, Tight Junction Proteins/metabolism, Tight Junctions/metabolism, Tight Junctions/pathology
Pubmed
Web of science
Open Access
Oui
Création de la notice
26/01/2015 10:33
Dernière modification de la notice
09/05/2019 1:15
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