MOLECULAR CONTROL OF EPITHELIAL BARRIER DYNAMICS AND REPAIR

Epithelial cells form dynamic barriers that are maintained by highly organized intercellular junctions, including tight junctions (TJs), adherens junctions (AJs), and desmosomes (DMs). These complexes provide structural adhesion while functioning as signaling hubs that regulate permeability, polarity, and epithelial responses to physiological and inflammatory cues. Junctional proteins undergo continuous remodeling during differentiation, stress, and immune activation, and their dysregulation contributes to barrier dysfunction in inflammatory diseases, ischemia, and cancer. This review highlights advances in defining the molecular architecture, signaling roles, and inflammation-induced remodeling of intestinal junctional proteins, incorporating key contributions from our group. In parallel, we summarize how epithelial cells activate specialized repair programs following injury and integrate leukocyte-derived protein and lipid mediators to coordinate mucosal wound closure. Finally, we discuss emerging regenerative engineering approaches, including synthetic hydrogels that support human intestinal organoids and nanoparticle delivery of pro-repair molecules, which provide new opportunities to restore epithelial integrity in chronic mucosal disease.