Cadherins as Central Modulators of Wound Repair

Tissue repair following injury requires the activation and coordinated modulation of multiple cell types. In the epidermis of the skin, as well as in other tissues with epithelial cell components, efficient wound healing requires complex regulation of cell-cell adhesions. In particular, cadherin-based cell-cell adhesions in epidermal keratinocytes and other epithelial cells are constantly remodeled during wound repair, to allow collective cell migration and efficient re-epithelialization of the wound. The two major types of cadherin-based adhesions found in the epidermis are adherens junctions and desmosomes, composed of classical and desmosomal cadherins, respectively. Cadherins are transmembrane proteins that join neighboring cells, functionally linking their intracellular cytoskeletons. Cadherin-based adhesions are indispensable to transduce mechanical forces and signaling events during wound healing. The pivotal role of cadherin-based adhesions in tissue regeneration after injury is emphasized by the observed defects in cutaneous wound healing and development of chronic wounds that result from loss or abnormal signaling of cadherin-based adhesion protein components.