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The ZO-1/DSC2/OCLN/CLDN3 protein set constitutes the core components of the apical junctional complex (AJC), which is essential for maintaining the selective permeability of epithelial and endothelial barriers (Frontiers in Pharmacology, 2022; Journal of Cell Science, 2013). This group comprises Zonula occludens-1 (ZO-1), a key scaffolding protein; Desmocollin-2 (DSC2), a desmosomal adhesion molecule; and the tight junction proteins Occludin (OCLN) and Claudin-3 (CLDN3, frequently mislabeled as CLN3 in some literature) (Cell, 2006; Frontiers in Pharmacology, 2022). These proteins work in concert to seal the paracellular space, regulate the flux of ions and solutes, and provide mechanical strength to tissues (Molecular Biology of the Cell, 2012). In clinical contexts, the downregulation or mislocalization of these proteins is a hallmark of barrier dysfunction, often referred to as "leaky gut," which underlies conditions like inflammatory bowel disease, celiac disease, and functional dyspepsia (Frontiers in Pharmacology, 2022). Furthermore, the loss of these junctional proteins is a critical step in the epithelial-mesenchymal transition (EMT) during cancer progression, facilitating tumor cell invasion and metastasis. Therapeutic agents such as larazotide acetate and certain glucocorticoids target these pathways to stabilize the AJC and restore barrier integrity, thereby reducing chronic inflammation and preventing disease progression (Journal of Cell Science, 2013).
Stabilization of the apical junctional complex and upregulation of tight junction and desmosomal protein expression to restore epithelial barrier integrity and reduce paracellular permeability.
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