IN-VIVO STIMULATION OF CONNECTIVE-TISSUE ACCUMULATION BY THE TRIPEPTIDE COPPER COMPLEX GLYCYL-L-HISTIDYL-L-LYSINE-CU2+ IN RAT EXPERIMENTAL WOUNDS

The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu) was first described as a growth factor for differentiated cells. Rece nt in vitro data showed that it possesses several properties of a pote ntial activator of wound repair. We investigated the effects of GHK-Cu in vivo, using the wound chamber model described previously (Schillin g, J. A., W. Joel, and M. T. Shurley, 1959. Surgery [St. Louis]. 46:70 2-710). Stainless steel wire mesh cylinders were implanted subcutaneou sly on the back of rats. The animals were divided into groups that rec eived sequential injections into the wound chamber of either saline (c ontrol group) or various concentrations of GHK-Cu. At the end of the e xperiments, rats were killed, wound chambers were collected, and their content was analyzed for dry weight, total proteins, collagen, DNA, e lastin, glycosaminoglycans, and specific mRNAs for collagens and TGFbe ta. In the GHK-Cu-injected wound chambers, a concentration-dependent i ncrease of dry weight, DNA, total protein, collagen, and glycosaminogl ycan contents was found. The stimulation of collagen synthesis was twi ce that of noncollagen proteins. Type I and type III collagen mRNAs we re increased but not TGFbeta mRNAs. An increase of the relative amount of dermatan sulfate was also found. A control tripeptide, L-glutamyl- L-histidyl-L-proline, had no significant effect. These results demonst rate that GHK-Cu is able to increase extracellular matrix accumulation in wounds in vivo.