Target intelligence / Profile preview

Epithelial tight junction complex (TJ)

Target
TJ
Molecular classification
Protein complex, Cell-cell junction, Cell adhesion molecule
01

Overview

Epithelial tight junction complexes, also known as zonula occludens, are specialized intercellular structures that form a selective barrier between adjacent epithelial cells, regulating the paracellular movement of solutes and preventing the entry of pathogens (Anderson & Van Itallie, 2009). These complexes are composed of transmembrane proteins such as claudins, occludin, and junctional adhesion molecules (JAMs), which are anchored to the actin cytoskeleton via scaffold proteins like zonula occludens (ZO-1, ZO-2, ZO-3) (Zihni et al., 2016). In diseases like inflammatory bowel disease and celiac disease, the breakdown of these junctions leads to increased intestinal permeability and chronic inflammation (Lee, 2015). Conversely, in oncology, the loss of tight junction integrity is often associated with epithelial-to-mesenchymal transition (EMT) and increased metastatic potential. Pharmacological targeting of tight junctions aims to either restore barrier function in inflammatory conditions, such as with the zonulin antagonist larazotide acetate, or transiently increase permeability to improve the delivery of large-molecule drugs across epithelial surfaces (Gopalakrishnan et al., 2012).

Other names
Zonula occludensTight junctionOccluding junctionIntercellular junctional complex
02

Mechanism of action

Modulation of paracellular permeability through the regulation of junctional protein assembly and disassembly, or direct binding to transmembrane components to alter barrier integrity (Gopalakrishnan et al., 2012; Maher et al., 2019).

03

Biological functions

Barrier functionParacellular transport regulationCell polarity maintenanceSignal transduction
04

Disease associations

Inflammatory bowel diseaseCeliac diseaseCancer metastasisInfectionAutoimmune disease
05

Safety considerations

Unintended systemic absorption of luminal toxinsPathogen translocationLoss of tissue compartmentalizationElectrolyte imbalance
06

Interacting drugs

Larazotide acetate

4 more in the full profile.

07

Biomarkers

Transepithelial electrical resistance (TEER)Zonulin levelsClaudin expression levelsOccludin expression levels

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