R. Hartwell, A. M. Rezakhanlou, A. Papp, M. Carr, A. Ghahary

Non-healing and chronic wounds affect 47 million patients each year in North America, a majority of whom are elderly. Wound healing is a complex and dynamic process that involves not only cell-cell communication in the form of signaling mediators, but also cell-matrix signaling. There is compelling evidence that an imbalance in any of these signaling events will lead to problematic healing. We have previously demonstrated that a keratinocyte derived anti-fibrogenic factor, 14-3-3 σ is a potent stimulator of matrix metalloproteinases, those of which are important for matrix remodeling in the later stages of normal wound healing. Additionally, our data has suggested that this factor is more expressed in non-proliferating (differentiated senescent) epithelial cells. Furthermore, It has been reported elsewhere that Hypoxic Inducible Factor-1 (HIF-1), a transcription factor that is important for neovascularization, migration and cell survival is involved in the pathology of aged, non-healing wounds and may be impaired as a result of senescence. Preliminary work from our lab has demonstrated that HIF-1 expression is decreased in fibroblasts co-cultured with confluent keratinocytes. It is our hypothesis that 14-3-3 σ expression is augmented in aged skin, relative to that of neonatal foreskin, and that its release affects not only matrix remodeling, but also other factors such as HIF-1. Comparison of these factors with age will be made by measuring relative abundance of mRNA and protein level for 14-3-3 σ, collagenase and HIF-1 in tissue biopsies from human subjects. We expect that an increased expression of 14-3-3 σ in aged skin may be suggestive of a thinner, weaker skin with a propensity for delayed healing and chronic wounds.

Keywords (Optional): 
Non-healing wounds
14-3-3 sigma
extracellular matrix