Stem cell recovering effect of copper‐free GHK in skin

Abstract

The peptide Gly-His-Lys (GHK) is a naturally occurring copper(II)-chelating motifs in human serum and cerebrospinal fluid. In industry, GHK (with or without copper) is used to make hair and skin care products. Copper-GHK plays a physiological role in the process of wound healing and tissue repair by stimulating collagen synthesis in fibroblasts. We also reported that copper-GHK promotes the survival of basal stem cells in the skin. However, the effects of copper-free GHK (GHK) have not been investigated well. In this study, the effects of GHK were studied using cultured normal human keratinocytes and skin equivalent (SE) models. In monolayer cultured keratinocytes, GHK increased the proliferation of keratinocytes. When GHK was added during the culture of SE models, the basal cells became more cuboidal than control model. In addition, there was linear and intense staining of α6 and β1 integrin along the basement membrane. The number of p63 and proliferating cell nuclear antigen positive cells was also significantly increased in GHK-treated SEs than in control SEs. Western blot and slide culture experiment showed that GHK increased the expression of integrin by keratinocytes. All these results showed that GHK increased the stemness and proliferative potential of epidermal basal cells, which is associated with increased expression of integrin. In conclusion, copper-free GHK showed similar effects with copper-GHK. Thus, it can be said that copper-free GHK can be used in industry to obtain the effects of copper-GHK in vivo. Further study is necessary to explore the relationship between copper-free GHK and copper-GHK.

GHK‐Cu‐liposomes accelerate scald wound healing in mice by promoting cell proliferation and angiogenesis

“…Peled et al claimed that GHK increases proliferation of stem cells, while GHK‐Cu increases their progression into differentiated cells . Choi et al showed that GHK promotes the survival of basal stem cells in a skin equivalent model, and that the number of proliferating cells is also increased by the addition of GHK . The additional function of GHK‐Cu‐liposomes we found in this study was to enhance HUVECs proliferation by 33.1% compared with GHK‐Cu.…”

“…22,23 Choi et al showed that GHK promotes the survival of basal stem cells in a skin equivalent model, and that the number of proliferating cells is also increased by the addition of GHK. 6 The additional function of GHK-Cu-liposomes we found in this study was to enhance HUVECs proliferation by 33.1% compared with GHK-Cu. ICP results indicated that although the Cu content delivered by GHK-Cu-liposomes is higher than that by free GHK-Cu, there is no big difference for the GHK-Cu uptake after 24 hours with liposome encapsulation.…”

“…In addition to regulating genes involved in wound healing and skin remodeling, GHK also increases the production of collagen, dermatan sulfate, chondroitin sulfate, and the small proteoglycan, decorin . Proliferative markers of epidermal stem cells, integrins and p63 were stimulated by GHK‐Cu and GHK at low concentrations …”

“…4 Proliferative markers of epidermal stem cells, integrins and p63 were stimulated by GHK-Cu and GHK at low concentrations. 5,6 Bacterial biofilms secrete powerful proteases that can degrade peptides in minutes. In diabetic and venous stasis skin ulcers, GHK is broken down quickly.…”

The Effect of the Human Plasma Molecule GHK-Cu on Stem Cell Actions and Expression of Relevant Genes

“…Epidermal cells became more cuboidal, as is characteristic for stem cells. The authors concluded that GHK and GHK-Cu increased epidermal cell stemness and keratinocyte proliferation, also increasing p63 and integrin expression [48,49].…”