Intestinal epithelial tight junction (TJ) (TJ)

The intestinal epithelial tight junction (TJ) is a multi-protein complex that forms a continuous seal between adjacent epithelial cells, serving as the primary determinant of the paracellular pathway's permeability (Lee, 2015, NIH/PMC4606628). It is composed of transmembrane proteins such as claudins, occludin, and junctional adhesion molecules (JAMs), which are anchored to the actin cytoskeleton via peripheral membrane proteins like zonula occludens (ZO-1, ZO-2, and ZO-3) (Zihni et al., 2016, Nature Reviews Molecular Cell Biology). Biologically, these junctions regulate the selective passage of ions, water, and nutrients while preventing the entry of pathogens and toxins into the systemic circulation (Fasano, 2011, Physiological Reviews). Dysregulation of tight junction integrity, often referred to as "leaky gut," is a hallmark of various gastrointestinal and systemic inflammatory diseases, including celiac disease and inflammatory bowel disease (IBD) (Chelakkot et al., 2018, Experimental & Molecular Medicine). Therapeutic strategies targeting these junctions aim to either restore barrier function in chronic inflammatory states or transiently increase permeability to facilitate the oral delivery of macromolecular drugs (Gopalakrishnan et al., 2012, J. Med. Chem.). For instance, larazotide acetate acts as a tight junction regulator by inhibiting the action of zonulin, thereby preventing the breakdown of these critical cellular seals (Fasano, 2020, F1000Research).

Other names

Zonula occludensParacellular barrierIntestinal barrierTight junction complex

Modulation of tight junction assembly and disassembly to regulate paracellular permeability, either by inhibiting zonulin-induced breakdown of the junctional complex or by enhancing the expression and localization of sealing proteins like claudin-1 and occludin (Fasano, 2011, Physiological Reviews; Lee, 2015, NIH/PMC4606628).