title: Connexin 26-mediated gap junctional intercellular communication suppresses paracellular permeability of human intestinal epithelial cell monolayers.
abstract: In some cell types, gap junctional intercellular communication (GJIC) is associated with tight junctions. The present study was performed to determine the roles of GJIC in regulation of the barrier function of tight junctions. Caco-2 human colonic cells were used as a monolayer model, and barrier function was monitored by measuring mannitol permeability and transepithelial electrical resistance (TER). The monolayers were chemically disrupted by treatment with oleic acid and taurocholic acid. Western blotting analyses were performed to evaluate the protein levels of connexins, which are components of gap junctional intercellular channels. Cx26 expression was detected in preconfluent Caco-2 cells, and its level increased gradually after the monolayer reached confluency. These results prompted us to examine whether overexpression of Cx26 affects barrier function. Monolayers of Caco-2 cells stably expressing Cx26 showed significantly lower mannitol permeability and higher TER than mock transfectants when the monolayers were chemically disrupted. The levels of claudin-4, an important component of tight junctions, were significantly increased in the stable Cx26 transfectant. These results suggest that Cx26-mediated GJIC may play a crucial role in enhancing the barrier function of Caco-2 cell monolayers.
authors.affiliation: Clinical Cell Biology (F5), Graduate School of Medicine, Chiba University, 260-8670, Chuo-Ward, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Morita
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Katsuno
authors.forename: Aihiro
authors.initials: A
authors.lastname: Hoshimoto
authors.forename: Noriaki
authors.initials: N
authors.lastname: Hirano
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saito
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Suzuki
mesh_terms: D018938:Caco-2 Cells; D002450:Cell Communication / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000502:physiology*; D062506:Claudin-4; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008353:Mannitol / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D019301:Oleic Acid / Q000494:pharmacology; D013656:Taurocholic Acid / Q000494:pharmacology; D019108:Tight Junctions / Q000378:metabolism* / Q000648:ultrastructure; D014162:Transfection; D015854:Up-Regulation / Q000502:physiology
chemical_list: C568157:CLDN4 protein, human; D062506:Claudin-4; D017630:Connexins; C000607042:GJB2 protein, human; D008565:Membrane Proteins; D000072259:Connexin 26; D019301:Oleic Acid; D008353:Mannitol; D013656:Taurocholic Acid