HYPOXIA INCREASES HUMAN KERATINOCYTE MOTILITY ON CONNECTIVE-TISSUE

Re-epithelialization of skin wounds depends upon the migration of kera tinocytes from the cut margins of the wound and is enhanced when human keratinocytes are covered with occlusive dressings that induce hypoxi a. In this study, two independent migration assays were used to compar e cellular motility on connective tissue components under normoxic or hypoxic conditions. Human keratinocytes apposed to collagens or fibron ectin exhibited increased motility when subjected to hypoxic (0.2 or 2 % oxygen) conditions compared with normoxic (9 or 20% oxygen) conditio ns. When compared with normoxic cells, hypoxic keratinocytes exhibited increased expression and redistribution of the lamellipodia-associate d proteins (ezrin, radixin, and moesin), Furthermore, hypoxic keratino cytes demonstrated decreased secretion of laminin-5, a laminin isoform known to inhibit keratinocyte motility. Hypoxia did not alter the num ber of integrin receptors on the cell surface, but did induce enhanced secretion of the 92-kD type IV collagenase. These data demonstrate th at hypoxia promotes human keratinocyte motility on connective tissue, Hypoxia-driven motility is associated with increased expression of lam ellipodia proteins, increased expression of collagenase and decreased expression of laminin-5, the locomotion brake for keratinocytes.