Occludin as a possible determinant of tight junction permeability in endothelial cells

TLDR

Endothelial tight junctions vary widely in permeability across tissues, and the molecular basis for this difference, particularly the role of the transmembrane protein occludin, remains unclear. Immunocytochemistry, immunoblotting, and mRNA analysis reveal that occludin is highly expressed and continuously distributed at brain endothelial cell contacts, whereas it is low and discontinuous in non‑neural endothelia and developmentally up‑regulated, indicating that occludin expression likely determines tight junction permeability.

Abstract

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.