The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ stimulates matrix metalloproteinase-2 expression by fibroblast cultures

Glycyl-histidyl-lysine-Cu2+ (GHK-Cu) is a tripeptide-copper complex known to be a potent wound healing agent. We previously showed its ability to stimulate in vitro and in vivo the synthesis of extracellular matrix components. The aim of this study was to determine the effects of GHK-Cu on MMP-2 synthesis by dermal fibroblasts in culture. We showed that GHK-Cu increased MMP-2 levels in conditioned media of cultured fibroblasts. This effect was reproduced by copper ions but not by the tripeptide GHK alone. This stimulation was accompanied by an increase of MMP-2 mRNA level. We also showed that GHK-Cu increased the secretion of the tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-2. Taken together, our results underline that GHK-Cu is not only an activator of connective tissue production but also of the remodeling of the extracellular matrix. It is able to modulate MMP expression by acting directly on wound ribroblasts. (C) 2000 Elsevier Science Inc. All rights reserved.