DEVELOPMENT OF AN IN VITRO WOUND HEALING MODEL

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The long term goal of this research project is to increase our understanding of the wound contraction process. A better understanding of contraction is an essential step in the search for therapeutic strategies necessary to contraction and scarring. Towards this goal, we have been studying several variations on an in vitro model of wound contraction. During the next five years, we plan an integrated approach in which we will use the in vitro wound contraction model to study cell signaling, regulation of contraction, and apoptosis. Specific Aim #1 focuses on the mitogen-activated protein kinase signal transduction pathways activated by stressed matrix contraction, autocrine regulation, and immediate early gene transcription. Specific Aim #2 focuses on the mechanisms responsible for stimulation of stressed and floating collagen contraction by platelet- derived growth factor and lysophosphatidic acid, differences in the regulation of floating and stressed matrix contraction, and the role of mechanical stress in myofibroblast differentiation. Specific Aim #3 focuses on the factors that contribute to apoptosis of cells undergoing stresses matrix contraction.