UP-REGULATION OF ALPHA(9) INTEGRIN AND TENASCIN DURING EPITHELIAL REGENERATION AFTER DEBRIDEMENT IN THE CORNEA

Stratified epithelia are exposed to abrasive forces and are required t o respond rapidly to injury to minimize fluid loss and the risk for mi crobial infection. Healing involves a cell migratory phase to reestabl ish barrier function and cell proliferation to restratify the epitheli um. Cell migration during re-epithelialization involves cell sliding, termed sheet movement, during which cells retain their cell-cell junct ions while dynamically altering their shape and cell-substrate interac tions to permit movement across the exposed wound bed, Proteins of the integrin family of receptor molecules modulate cell shape, cell migra tion, and signal transduction in many cell types. In epithelial cells, integrins of the beta(1) family have been implicated in regulating ce ll proliferation and differentiation. alpha(9) beta b(1) is one of the newer members of the integrin beta(1) family and has been recently sh own to function as a tenascin receptor. Although little is known about its function in vivo, studies in developing mouse cornea and eyelid s uggest that it may play a role in epithelial differentiation. Using a debridement wound model in the mouse cornea, we show in this study tha t (a) in response to small debridement wounds that close without cell proliferation, alpha(9) integrin protein and mRNA are not induced duri ng migration but are induced during restratification, (b) larger debri dement wounds that require cell proliferation to generate the cells ne cessary for sheet movement result in a dramatic induction of alpha(9) protein and its mRNA during both migration and restratification, and ( c) tenascin, an alpha(9) beta(1) ligand, accumulates beneath epithelia l cells during restratification but not during cell migration. Therefo re, alpha(9) integrin protein production and tenascin accumulation are dynamically regulated in response to corneal epithelial injury.