Modulation of epithelial cell adhesion in gastrointestinal homeostasis

Cell-cell and cell-matrix interactions are critical to the dynamic processes necessary for tissue morphogenesis in embryos and to the maintenance of complex differentiated tissues in adult organisms. The E- cadherin-catenin and integrin complexes influence and coordinate a variety of cellular processes including adhesion, differentiation, polarity, migration, proliferation, and survival. The suggestion of molecular cross-talk between the cadherin- and integrin-mediated cell adhesion systems, as well as the catenin and EGFR signaling pathways, during the regulation of such cellular processes has important implications for the understanding of gastrointestinal epithelial cell biology. It is therefore not surprising that adhesion-associated molecules are common targets for motogenic and mitogenic factors. The modulation of perturbation of cadherin, catenin, and integrin expression and function play a central role in gastrointestinal epithelial homeostasis and in various pathophysiological situations such as the repair of mucosal injury by epithelial restitution. This implies the potential for the clinical and pharmacological management of chronic ulcerative and inflammatory lesions through the manipulation of cellular adhesive mechanisms. However, to validate such an approach we need appropriate animal models which more closely mimic human gastrointestinal disease. Further development and refinement of such models combined with the elucidation of the biochemical and genetic processes involved will allow investigation into novel treatment, management, and prevention protocols.