Chapter 10 Dynamics of Intestinal Epithelial Tight Junctions

Abstract

Publisher Summary Tight junctions in this epithelium are crucial to barrier function and may be regulated and such regulation plays a role in the uptake of nutrients. Given the plasticity of the tight junction in health, studies suggest that this structure may be functionally altered in disease states, even when the epithelium remains confluent. This chapter discusses tight junctions (zonula occludens (ZO)), as potentially regulated barriers, intestinal ZO, as a regulated transport pathway, and its function in disease states. There exist two pathways for passive permeation across intestinal epithelia: the paracellular or the transcellular pathways. The paracellular pathway is composed of the tight junction— that is, the ZO and the underlying intercellular space. The ZO consists of a belt that wraps the epithelial cells at the apical pole. Within this belt, the lateral membranes of adjacent cells are focally fused and these fusion points circumferentially belt the apex of the cell in an anasomosing fashion. Cytoskeleton may be involved in transducing the signals that lead to ZO alterations. Actin microfilaments associate with the ZO-associated peripheral plaque-like condensations, so ZO could be more directly affected by the cytoskeleton. Nutrient exposure alters ZO permeability and provides an additional (paracellular) pathway for nutrient absorption. Using T 84 monolayers of model intestinal epithelia studies have been carried out in hopes of modeling disease-related phenomena for mechanistic studies. T 84 cells grow as confluent monolayers, display high baseline resistance, and have ZOs with subunit structure–function correlates not dissimilar to those seen in native intestinal epithelium.