CD44 MEDIATED FIBROBLAST MIGRATION IN A WOUND MODEL

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The primary objective of this project is to examine the mechanisms by which the CD44 cell surface receptor mediates human dermal fibroblast migration into the provisional fibrin matrix. Wound healing is a finely organized cascade of events involving the interactions of a variety of cell types, growth factors, and extracellular matrix proteins. In addition to providing hemostasis and protection, the fibrin plug which forms immediately upon wounding serves as a lattice on which fibroblasts migrate to begin the healing process. Studies of human alveolar fibroblasts derived from patients with acute lung injury implicate the CD44 cell surface receptor in invasion of the provisional matrix. CD44 is a family of cell surface receptors implicated in lymphocyte homing as well as tumor cell migration and metastasis. The integrin cell surface receptors have been implicated in human dermal fibroblast invasion of the provisional wound matrix; however, the role of CD44 in the mechanism of dermal fibroblast migration is unknown. This proposal will test the hypothesis that CD44 is a mediator of human dermal fibroblast migration into the provisional wound matrix. The study will examine: 1. CD44-mediated dermal fibroblast adhesion to various provisional matrix components; 2. CD44-mediated dermal fibroblast migration along provisional matrix components; and 3. CD44-mediated dermal fibroblast invasion of a fibrin gel. Understanding the mechanisms of fibroblast migration will provide a basis for the development of novel therapies in the treatment of fibrotic disorders.