Targeting Epithelial Cell Migration to Accelerate Wound Healing

Successful wound healing requires the recruitment and migration of distinct cell types to the wound followed by re-epithelialization of the surface of injured tissue. Interventions that enhance the migration of effector cells to the site and temporally increase epithelialization can be clinically relevant. Cell attachment and adhesion molecules necessary for cell migration include all four members of the RIPP complex, consisting of the proteins Rsu1, Integrin Linked Kinase ILK, PINCH, and Parvin. The correct association of these proteins in a functional complex depends on their phosphorylation by serine threonine kinases of the protein kinase C PKC family and the process can be enhanced or inhibited by modulating the levels of the RIPP complex proteins as well by regulating their serine and threonine phosphorylation. Our data indicate that the expression of the RIPP proteins is required for migration of human keratinocyte cell line in vitro. In addition, the phosphorylation of RIPP proteins contributes to their association and complex formation. For Rsu1- the sites include serine 264 and 268. Formation of the RIPP complex depends on appropriate signals that derive from cell adhesion including from PKC pathway and, hence, the inhibition of PKC blocks Rsu1-PINCH1 association, PINCH1-ILK association, and cell migration. Depletion of RIPP proteins also results in activation of PKA signaling and consequent disruption of regulatory networks impacting integrin function and actin polymerization.