In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds.
Open accessAbstract
The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu) was first described as a growth factor for differentiated cells. Recent in vitro data showed that it possesses several properties of a potential activator of wound repair. We investigated the effects of GHK-Cu in vivo, using the wound chamber model described previously (Schilling, J.A., W. Joel, and M.T. Shurley, 1959. Surgery [St. Louis]. 46:702-710). Stainless steel wire mesh cylinders were implanted subcutaneously on the back of rats. The animals were divided into groups that received sequential injections into the wound chamber of either saline (control group) or various concentrations of GHK-Cu. At the end of the experiments, rats were killed, wound chambers were collected, and their content was analyzed for dry weight, total proteins, collagen, DNA, elastin, glycosaminoglycans, and specific mRNAs for collagens and TGF beta. In the GHK-Cu-injected wound chambers, a concentration-dependent increase of dry weight, DNA, total protein, collagen, and glycosaminoglycan contents was found. The stimulation of collagen synthesis was twice that of noncollagen proteins. Type I and type III collagen mRNAs were increased but not TGF beta 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 demonstrate that GHK-Cu is able to increase extracellular matrix accumulation in wounds in vivo.
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At low concentrations, GHK-Cu stimulates the migration of macrophages and mast cells.
“GHK-Cu at low concentrations is a powerful attractant for capillary cells that build new blood vessels, and a powerful migration stimulant for macrophages and mast cells that remove damaged cellular debris and secrete proteins important for wound contraction and tissue healing [8–9].”
From The potential of GHK as an anti-aging peptide (2020) · cites this paper as [9]
The Introduction says GHK-Cu is a potent chemotactic agent for monocytes/macrophages and mast cells, supporting the migration claim. It does not specify that this effect occurs at low concentrations; the paper’s dose-response results concern connective-tissue accumulation, not migration. (LLM, conf=0.84)
Experimental — accuracy not yet measuredAt low concentrations, GHK-Cu attracts capillary cells that form new blood vessels.
“GHK-Cu at low concentrations is a powerful attractant for capillary cells that build new blood vessels, and a powerful migration stimulant for macrophages and mast cells that remove damaged cellular debris and secrete proteins important for wound contraction and tissue healing [8–9].”
From The potential of GHK as an anti-aging peptide (2020) · cites this paper as [9]
The Discussion describes GHK-Cu as a potent chemoattractant for endothelial cells, and the Introduction reports that it can trigger angiogenesis in vivo. The paper does not say that the attraction occurs at low concentrations; its dose results concern connective-tissue accumulation, not endothelial-cell attraction. (LLM, conf=0.86)
Experimental — accuracy not yet measuredGHK-Cu increased collagen I and collagen III expression when injected in experimental wounds in rats, with increase detected on day 3 and persisting until day 14.
“In another study, the same group established that GHK-Cu increased collagen I and collagen III expression when injected in experimental wounds in rats.The increase was detected in the samples collected on day 3 and persisted until day 14.”
From GHK-Cu may Prevent Oxidative Stress in Skin by Regulating Copper and Modifying Expression of Numerous Antioxidant Genes (2015) · cites this paper as [24]
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“Since copper is an important trace element that plays a key factor in the production of collagen and elastin, GHK-Cu can be a natural supplement for copper in the connective tissue synthesis [10-11].”
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- Authors
- Maquart, F. X., Bellon, G., Chaqour, B., Wegrowski, J., Patt, L. M., Trachy, R. E., Monboisse, J. C., Chastang, F., Birembaut, P., & Gillery, P.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Venue
- Journal of Clinical Investigation
- Published
- 1993-11-01
- Volume
- 92
- Issue
- 5
- Pages
- 2368-2376
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC288419
- OpenAlex
- W2080794445
- Semantic Scholar
- 24f444b64fa14fa56c7430a1c0f6dc937336f8e5
- Cited by
- 110
- References
- 36
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 2 · 2023: 5 · 2022: 2 · 2021: 1 · 2020: 5 · 2019: 3 · 2018: 4 · 2017: 2 · 2016: 6 · 2015: 8 · 2014: 8 · 2013: 3 · 2012: 4
- FWCI
- 3.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Centre National de la Recherche Scientifique
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Dermatology › Dermatologic Treatments and Research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- GHK-Cu, wound healing, extracellular matrix, collagen synthesis, type I collagen, type III collagen, dermatan sulfate, glycosaminoglycans, TGF-beta
- MeSH terms
- Animals, Collagen, Connective Tissue, Copper, Dermatan Sulfate, Dose-Response Relationship, Drug, Growth Substances, Male, Oligopeptides, RNA, Messenger, Skin, Wound Healing, Diffusion Chambers, Culture, Gene Expression, Rats, Sprague-Dawley, Rats
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