Epithelial tight junction barrier (TJ)

The epithelial tight junction barrier is a multi-protein complex located at the apical-most part of the lateral intercellular space between epithelial cells. It serves as a primary regulator of the paracellular pathway, controlling the passage of ions, water, and solutes while preventing the translocation of pathogens and toxins (Anderson & Van Itallie, 2009). The structure is composed of transmembrane proteins, including claudins, occludin, and junctional adhesion molecules (JAMs), which interact with intracellular scaffold proteins like zonula occludens (ZO-1) to link the junction to the actin cytoskeleton (Buckley & Turner, 2018). In addition to its gate function, it acts as a fence to maintain cell polarity by separating the apical and basolateral membrane domains. Pathological disruption of the tight junction barrier, often referred to as leaky gut, is implicated in the pathogenesis of various autoimmune and inflammatory diseases, such as celiac disease and inflammatory bowel disease (Fasano, 2011). Therapeutic interventions like larazotide acetate aim to stabilize these junctions or inhibit the signaling pathways that lead to their breakdown, thereby restoring intestinal homeostasis and preventing the entry of inflammatory triggers (Gopalakrishnan et al., 2012).

Other names

Zonula occludensTight junctionIntercellular junctional complexPermeability barrier

Modulation of paracellular permeability through the antagonism of zonulin signaling, stabilization of transmembrane proteins like claudins and occludin, or the regulation of the perijunctional actomyosin ring to restore or transiently open the barrier.