Ephrin-Eph signaling: an important regulator of epithelial integrity and barrier function

Eph receptor-interacting proteins (ephrin) ligands and their erythropoietin-producing human hepatocellular (Eph) receptors elicit bidirectional signals that regulate cell migration, angiogenesis, neuronal plasticity, and other developmental processes in the embryo. In adulthood, ephrin-Eph signaling regulates numerous homeostatic events, including epithelial cell proliferation and differentiation. Epithelial surfaces, including those of skin and vagina, are lined by layers of stratified squamous epithelium (SSE) that protect against mechanical stress and microbial pathogen invasion. Ephrin-Eph signaling is known to promote cutaneous epithelial barrier function by regulating the expression of specialized cell-cell adhesion junctions termed desmosomes, but the role of this signaling system in maintaining epithelial integrity and barrier function in the vagina is less explored. This review summarizes current understanding of ephrin-Eph signaling that regulates desmosome expression and barrier function in the skin and considers evidence that suggests ephrin-Eph signaling similarly regulates these processes in vaginal SSE.