title: Occludin as a possible determinant of tight junction permeability in endothelial cells.
abstract: Endothelial cells provide a crucial interface between blood and tissue environments. Free diffusion of substances across endothelia is prevented by the endothelial tight junction, the permeability of which varies enormously depending on tissue. Endothelial cells of the blood-brain barrier possess tight junctions of severely limited permeability, whereas those of non-neural tissue are considerably leakier, but the molecular basis for this difference is not clear. Occludin is a major transmembrane protein localizing at the tight junction. In this study, we show, by immunocytochemistry, that occludin is present at high levels and is distributed continuously at cell-cell contacts in brain endothelial cells. In contrast, endothelial cells of non-neural tissue have a much lower expression of occludin, which is distributed in a discontinuous fashion at cell-cell contacts. The apparent differences in occludin expression levels were directly confirmed by immunoblotting. The differences in occludin protein were reflected at the message level, suggesting transcriptional regulation of expression. We also show that occludin expression is developmentally regulated, being low in rat brain endothelial cells at postnatal day 8 but clearly detectable at post-natal day 70. Our data indicate that regulation of occludin expression may be a crucial determinant of the tight junction permeability properties of endothelial cells in different tissues.
authors.affiliation: Eisai London Research Laboratories Ltd, University College London, UK.
authors.forename: T
authors.initials: T
authors.lastname: Hirase
authors.forename: J M
authors.initials: JM
authors.lastname: Staddon
authors.forename: M
authors.initials: M
authors.lastname: Saitou
authors.forename: Y
authors.initials: Y
authors.lastname: Ando-Akatsuka
authors.forename: M
authors.initials: M
authors.lastname: Itoh
authors.forename: M
authors.initials: M
authors.lastname: Furuse
authors.forename: K
authors.initials: K
authors.lastname: Fujimoto
authors.forename: S
authors.initials: S
authors.lastname: Tsukita
authors.forename: L L
authors.initials: LL
authors.lastname: Rubin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001253:Astrocytes; D001921:Brain / Q000098:blood supply* / Q000166:cytology / Q000254:growth & development; D015820:Cadherins / Q000032:analysis; D002196:Capillaries / Q000737:chemistry / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000502:physiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D003598:Cytoskeletal Proteins / Q000032:analysis; D004727:Endothelium / Q000166:cytology; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D005614:Freeze Fracturing; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006168:Guinea Pigs; D008565:Membrane Proteins / Q000032:analysis* / Q000235:genetics; D051379:Mice; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D062793:Occludin; D010750:Phosphoproteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D019108:Tight Junctions / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D015534:Trans-Activators; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin
chemical_list: C495267:CTNNB1 protein, mouse; D015820:Cadherins; C495268:Ctnnb1 protein, rat; D017077:Culture Media, Conditioned; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D062793:Occludin; C568986:Ocln protein, mouse; C568987:Ocln protein, rat; D010750:Phosphoproteins; D012333:RNA, Messenger; C569043:Tjp1 protein, mouse; C569044:Tjp1 protein, rat; D015534:Trans-Activators; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin