Expression of Glycosaminoglycans and Small Proteoglycans in Wounds: Modulation by the Tripeptide–Copper Complex Glycyl-L-Histidyl-L-Lysine-Cu2+

Abstract

Glycyl-histidyl-lysine-Cu(2+) is a tripeptide-copper complex previously shown to be an activator of wound healing. We have investigated the effects of glycyl-histidyl-lysine-Cu(2+) on the synthesis of glycosaminoglycans and small proteoglycans in a model of rat experimental wounds and in rat dermal fibroblast cultures. Repeated injections of glycyl-histidyl-lysine-Cu(2+) (2 mg per injection) stimulated the wound tissue production, as appreciated by dry weight and total protein measurements. This stimulation was accompanied by an increased production of type I collagen and glycosaminoglycans (assessed, respectively, by hydroxyproline and uronic acid contents of the chamber). Electrophoretic analysis of wound tissue glycosaminoglycans showed an accumulation of chondroitin sulfate and dermatan sulfate in control wound chambers, whereas the proportion of hyaluronic acid decreased with time. The accumulation of chondroitin sulfate and dermatan sulfate was enhanced by glycyl-histidyl-lysine-Cu(2+) treatment. The expression of two small proteoglycans of the dermis, decorin and biglycan, was analyzed by northern blot. The biglycan mRNA steady-state level in the chamber was maximal at day 12, whereas the decorin mRNA increased progressively until the end of the experiment (day 22). Glycyl-histidyl-lysine-Cu(2+) treatment increased the mRNA level of decorin and decreased those of biglycan. In dermal fibroblast cultures, the stimulation of decorin expression by glycyl-histidyl-lysine-Cu(2+) was also found. In contrast, biglycan expression was not modified. These results show that the expression of different proteoglycans in wound tissue are regulated in a different manner during wound healing. The glycyl-histidyl-lysine-Cu(2+) complex is able to modulate the expression of the extracellular matrix macromolecules differently during the wound repair process.

A Randomized, Open Label, Comparative Study of Lysine Cream With Standard Treatment in Patients With Second Degree Superficial Burns

“…Another study conducted by Faculty of Medicine at France with glycyl-L-histidyl-L-lysine showed that L-lysine significantly promoted wound healing [7] which is in accordance with this study. A small study conducted in our department in Grade 1 and 2 diabetic ulcers also showed that lysine promoted ulcer healing which also supports the wound healing property of L-lysine.…”

Aristolochia bracteolata Enhances Wound Healing in vitro through Anti-inflammatory and Proliferative Effect on Human Dermal Fibroblasts and Keratinocytes

“…MMP-2 is mainly expressed by fibroblasts. 25 All the MMPs are synthesized and released as zymogens called pro-MMP and need to be activated by proteolytic cleavage. In this study, we studied the expression and activation of MMP 2 using in vitro scratch wound model in human dermal fibroblast cell lines.…”

“…A small linear scratch was created in the confluent monolayer by gently scraping with sterile cell scrapper as per standard methods. 12 Cells were extensively rinsed with medium to remove cellular debris before treating with different concentrations (25,50, 100, 250 µg/mL) of plant extracts in FBS deprived condition. Epidermal growth factor (EGF) was used as positive control distinctly to judge the rate of cell migration.…”

“…26 Moreover, recent data showed that MMP-2 might be the enzyme first and foremost responsible for collagen degradation in tissues where a high extracellular matrix turnover is observed. 25 On the other hand, by its capability to degrade type IV collagen, MMP-2 could also participate in the basement membrane remodeling which occurs during angiogenesis. Taken together, our results demonstrate that MMP 2 is selectively expressed or activated at the successive periods of wound healing.…”

Ankaferd Blood Stopper (ABS) ve Topikal Tripeptid Bakır Kompleksinin (TCC) Ratlarda Yara İyileşmesi Üzerine Etkisi: Deneysel Çalışma

“…A synthetic form of GHK used in the preparation of the tripeptide-copper complex (TCC) acts as a controlled delivery system for copper to the wound site. Glycyl-L-histidyl-L-lysine-Cu +2 (GHK-Cu) is a TCC isolated from human plasma by Pickart and Thaler in 1973 [16][17][18] . The efficacy of TCC in acute wound healing is well established, and it possesses many properties that promote wound healing which include increase in neovascularization [19] , increase in epithelialization and collagen deposition [3,16,20] , acceleration of wound contraction [3,21,22] , and improvement of the acute wound environment by increasing proteinases [17] .…”