Interference with endogenous ras function inhibits cellular responses to wounding

Wounding of tissue induces cellular responses that ultimately result in wound repair. Studies in tissue culture model systems indicate that these responses include induction of AP-1 regulated genes, cell migration and mitogenesis which are also characteristic of cellular responses to growth factors. Investigations have identified cellular ras proteins as critical components of growth factor-stimulated signal transduction pathways, however their role in the wounding response is less clear. Investigation of the potential involvement of c-Ras in this process utilized quiescent living bovine corneal endothelium cells (BCE) which were microinjected with ras dominant interfering mutant protein (N17) and subsequently stimulated by mechanical wounding. Analysis of these cells demonstrated that microinjection of dominant-interfering ras protein, but not control proteins, inhibited the wounding response as evidenced by diminished Fos expression, lack of cell migration and a block in DNA synthesis.