Wound healing is a complex biological process that involves the coordinated participation of multiple cell types. Growth of new epithelium and connective tissue with coupled with sprouting of new blood vessels, or angiogenesis, to provide blood supply to the newly regenerated tissue. Impaired and delayed wound healing are significant problems in the elderly, a rapidly increasing segment of the population. Recently, a novel angiogenic factor, CYR61, which is highly induced in granulation tissues of healing wounds and is encoded by a growth factor-inducible immediately-early gene has been described. CYR61 is able to induce neovascularization in endothelial cells and to stimulate chemotaxis, proliferation and synthesis of proteins involved in matrix remodeling in fibroblasts It is hypothesized that inducible expression of CYR61 is compromised in the elderly, thus leading to impaired and delayed wound repair. This proposal seeks to test this hypothesis in two aims. First, the expression of CYUR61 will be examine din young and senescent human fibroblasts in culture, and in granulation tissue of young and aged mice undergoing cutaneous wound healing. Second, purified CYR61 protein will be applied to wounds in young and aged mice to assess whether healing will be promoted. These studies will yield information on the role of CYR61 in wound healing and provide insights into the potential of CYR61 as a therapeutic agents for wound healing in the elderly.
