The role of focal adhesion kinase in corneal epithelial wound healing

Given the importance in several cellular processes, including cell migration and proliferation, focal adhesion kinase (FAK) has attracted much interest on its role in physical and pathological relevance. The biological role of FAK is emerging to be elucidated due to the availability of genetic engineered mice, in particular the FAK floxed mice, by combining with and varied Cre mice, it allows us to examine the functionality of FAK in physiopathologic conditions which are precluded due to the embryonic lethality of the conventional FAK knockout. Taking advantage of the Cre/loxP driven FAK conditional knockout approach, we generated the K12-rtTA/tetO-Cre/ FAK f/Δ triple transgenic mice to specifically delete FAK in corneal epithelial cells (CE-FAK), which consequently resulted in an impairment of corneal epithelial wound healing compared with the control mice. The impaired wound healing in corneal epithelial cells predominantly occurred in the earlier stage of the healing process in contrast to the prominent delay of wound healing in the late stage in AKT1-/- mice. Furthermore, the defect in the corneal epithelial wound healing of CE-FAK mice was reversed by infection/overexpression with adenovirus-bearing wild type FAK but not Y397F or FRNK mutant. In agreement with the above in vivo result, we also demonstrated several analogous in vitro results using human corneal epithelial cells (HCECs), highlighting that increased FAK expression and activation are concurrently associated with the promotion of cell adhesion and migration toward collagen IV and EGF. These results indicate a pivotal role for FAK and its mediated signaling in response to corneal epithelial wound stimuli to promote its healing. In addition, via applying several pharmacological inhibitors, such as PP2 (an Src inhibitor), SP600125, and SB203580, we also found that Src and p38 are potential downstream effectors of FAK-mediated wound healing in corneal epithelial cells in mice. Taken together, this study provides comprehensive data for an important role of FAK in corneal epithelial wound healing and underscores the need for FAK in physiopathological maintenance.