Effect of GLY-HIS-LYS and its copper complex on TGF-β secretion in normal human dermal fibroblasts.

Transforming growth factor β (TGF-β) is a cytokine involved in a wide variety of biological process- es such as cell growth, differentiation and proliferation, apoptosis and regulation of the immune response. It has an important role in wound healing process, fibrosis and scar tissue formation. Similarly to TGF-β1, insulin growth factor (IGF) family is expressed locally in response to tissue injury. Treatment of dermal fibroblasts with IGF-1 caused a substantial induction of TGF-β1 mRNA. Not a great deal of research so far has focused on IGF-2. Much attention has been focused on the tripeptides such as Gly-His-Lys (GHK) and their copper complexes, which have a high activity and good skin tolerance. Recent data suggest that their physiological role has been related to the process of wound healing, tissue repair and skin inflammation. In the present study, the influence of 1 nM solutions of GHK, GHK-Cu and CuCl2, on IGF-2-dependent TGF-β1 secretion in normal human dermal fibroblasts cells was investigated. Fibroblasts were cultured in 24-well plates. Total TGF-β1 pro- tein was evaluated using the ELISA kit. The Bradford reagent was used to determine the total quantity of cel- lular protein. Treatment of fibroblasts with 100 ng/mL IGF-2 resulted in a significant increase in TGF-β1 secretion. GHK and its copper complex and free copper ions decreased IGF-2-dependent TGF-β1 secretion. Our observations provide some new information on the potential use of that peptide contained in cosmetics to treat and prevent the formation of hypertrophic scars.