Upregulation of α9 integrin and tenascin during epithelial regeneration after debridement in the cornea

Abstract

Stratified epithelia are exposed to abrasive forces and are required to respond rapidly to injury to minimize fluid loss and the risk for microbial infection. Healing involves a cell migratory phase to reestablish barrier function and cell proliferation to restratify the epithelium. Cell migration during re-epithelialization involves cell sliding, termed sheet movement, during which cells retain their cell-cell junctions while dynamically altering their shape and cell-substrate interactions to permit movement across the exposed wound bed. Proteins of the integrin family of receptor molecules modulate cell shape, cell migration, and signal transduction in many cell types. In epithelial cells, integrins of the β1 family have been implicated in regulating cell proliferation and differentiation, α9b1 is one of the newer members of the integrin β1 family and has been recently shown to function as a tenascin receptor. Although little is known about its function in vivo, studies in developing mouse cornea and eyelid suggest that it may play a role in epithelial differentiation. Using a debridement wound model in the mouse cornea, we show in this study that (a) in response to small debridement wounds that close without cell proliferation, α9 integrin protein and mRNA are not induced during migration but are induced during restratification, (b) larger debridement wounds that require cell proliferation to generate the cells necessary for sheet movement result in a dramatic induction of α9 protein and its mRNA during both migration and restratification, and (c) tenascin, an α9β1 ligand, accumulates beneath epithelial cells during restratification but not during cell migration. Therefore, α9 integrin protein production and tenascin accumulation are dynamically regulated in response to corneal epithelial injury.