Characterization of Changes in Hyaluronan Following Epidermal Barrier Injury in an Organotypic Model

The stratum corneum, the outermost layer of the epidermis of skin, provides a functional permeability barrier that is essential for our survival and must be rapidly repaired after injury. Of interest to us, a ubiquitous matrix molecule called hyaluronan (HA) has come to the forefront in wound healing research because it is induced after epidermal injury and may be crucial for barrier repair. This thesis examines the role of HA during recovery from the most fundamental form of skin injury, i.e. selective damage to the stratum corneum. The overall question is whether this form of stratum corneum injury can lead to changes in HA similar to that of a full thickness skin wound. To investigate this question, a bioengineered model of barrier injury in organotypic epidermal cultures was first characterized. Changes in HA, in terms of an increase in overall amount and molecular weight, and increased levels of the HA-metabolizing enzymes (HA Synthases 2 and 3) were then measured and defined. Finally, the signalling mechanisms responsible for induction of HA synthesis were explored, revealing that activation of the Epidermal Growth Factor Receptor is essential for the up-regulation of HA after barrier injur