EPIDERMAL GROWTH FACTOR STIMULATES WOUND HEALING IN VIVO

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DESCRIPTION: (Adapted from the applicant's abstract) Growth control mechanisms in cutaneous wound healing are the central focus of this project. Now that in vivo studies with various exogenous growth factor shave shown a biological impact on general wound repair processes, it is timely to dissect and define signalling mechanisms of cytokines and their receptors on discrete wound healing processes such askeratinocyte proliferation, migration, recruitment of inflammatory populations and extracellular matrix proteins. EGF and EGF-like ligands, their common receptor (EGF-r tyrosinekinase), and subsequent phosphorylated substrates will be studied within unique wound healing environments. Transcription of EGF like ligands and their receptor (EGF-r) will be investigated using in situ hybridization and Northern blot analysis, protein deposition will be examined using immunohistochemical staining, and binding status will be studied with autoradiography. To define epidermal wounding responses, the EGF signalling cascade will be compared in migrating and proliferating populations of wound keratinocytes, both in vitro and in an in vivo model of superficial trauma (mouse tail tape stripping). Deeper wound environments (excisional porcine wounds, human burns, human chronic wounds) will be utilized to define and contrast cytokine mechanisms which control the extracellular matrix proteins. In addition, the balance between stimulatory cytokines(EGF) and inhibitory cytokines (TGFB superfamily-BMP4) will be examined using a BMP4 transgenic mouse wound model. Lastly, exogenously applied molecules relevant to the EGF signalling cascade will be used as experimental tools to modify epidermal and/or mesenchymal components of wound repair.