Target intelligence / Profile preview

Intestinal epithelial tight-junction protein (TJ) (TJ)

Target
TJ
Molecular classification
Cell adhesion molecule, Scaffolding protein, Transmembrane protein, Other
01

Overview

Intestinal epithelial tight-junction protein (TJ) refers to a complex network of transmembrane and cytosolic proteins that form a selective barrier between adjacent epithelial cells in the gut. This complex, which includes claudins, occludin, and zonula occludens (ZO) proteins, regulates the paracellular movement of water, ions, and nutrients while preventing the entry of pathogens and toxins from the lumen into the systemic circulation (Source: StatPearls, PMID: 30571025). Its primary biological role is to maintain the intestinal mucosal barrier and cell polarity (Source: NIH, PMID: 28123247). In pathological states like Celiac disease and Inflammatory Bowel Disease (IBD), the expression and localization of these proteins are disrupted, leading to increased intestinal permeability or "leaky gut" (Source: Frontiers in Immunology, PMID: 31275313). Pharmacological targeting of these proteins, such as with the zonulin antagonist larazotide acetate, aims to restore barrier integrity and mitigate autoimmune responses (Source: Journal of Pharmaceutical Sciences, PMID: 25611133). Additionally, temporary modulation of these proteins is explored as a strategy to enhance the oral bioavailability of poorly permeable drugs (Source: Advanced Drug Delivery Reviews, PMID: 23159811).

Other names
Tight junction complexZonula occludensParacellular barrier proteinsIntestinal barrier proteins
02

Mechanism of action

Antagonism of the zonulin receptor to prevent junction disassembly; upregulation of claudin and occludin expression to restore barrier integrity; stabilization of the perijunctional actin-myosin ring; activation of chloride channels to promote junctional assembly.

03

Biological functions

Barrier functionParacellular transportCell polaritySignal transductionOther
04

Disease associations

InflammationInfectionCeliac diseaseInflammatory Bowel DiseaseIrritable Bowel SyndromeOther
05

Safety considerations

Risk of non-specific permeability allowing pathogen or toxin entryPotential for systemic inflammationOff-target effects on other epithelial barriersElectrolyte imbalance
06

Interacting drugs

Larazotide acetate

5 more in the full profile.

07

Biomarkers

Serum zonulinLactulose-to-mannitol urinary ratioFecal calprotectinClaudin-3Intestinal fatty acid-binding protein (I-FABP)

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