Tag Archives: heparin-binding EGF-like growth factor
Efficacy of human heparin-binding EGF-like growth factor in healing experimental chemical burns
L. M. Dronko1, T. M. Lutsenko1*, O. I. Golembiovska1,
T. Yu. Trokhymchuk2, M. A. Arkhypova2, V. A. Dibrova2, Yu. V. Dibrova2,
S. L. Rybalko2, S. A. Myakushko3, A. A. Siromolot3,4, O. Yu. Galkin1,4
1National Technical University of Ukraine “Igor Sikorsky Kyiv Polytechnic Institute”, Kyiv;
2SІ “L.V. Gromashevskyi Institute of Epidemiology and Infectious Diseases
of the NAMS of Ukraine”, Kyiv, Ukraine;
3ESC “Institute of Biology and Medicine”, Taras Shevchenko National University of Kyiv, Ukraine;
4Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: lutsenko.tetiana@lll.kpi.ua
Received: 25 December 2024; Revised: 07 February 2025;
Accepted: 25 April 2025; Available on-line: 12 May 2025
According to the WHO, burns are the third most common cause of traumatic skin injuries. Chemical burns are characterized by a complex course and a long healing process. The use of the representatives of the epidermal growth factor family seems to be a promising direction in the treatment of chemical burns. The aim of this study was to evaluate the effectiveness of the recombinant human heparin-binding EGF-like growth factor (rhHB-EGF) in treating burn wounds in mice. The expression of a recombinant human HB-EGF analog was induced in the prokaryotic system E. coli BL21 Star, the protein was isolated, purified and its preparations in PBS or in a form of gel containing sodium hyaluronate and potassium sorbate were obtained. The burn wound was simulated in white non-inbred mice by subcutaneous injection of 10% paraformaldehyde solution, healing was observed for 17 days. The initial wound area was measured on the 7th day after the burn injury when the treatment was started. The mice with burn injury were divided into groups of 3 each – untreated mice (control), treated with different preparations: gel without rhHB-EGF; rhHB-EGF in a gel form; rhHB-EGF in PBS solution. The preparations (100 μl, 1.5 mg of rhHB-EGF) were applied to burn wounds daily for 5 days. Wound area, healing rate and histological patterns of skin samples were estimated. It was shown that groups with burn injury treated with HB-EGF protein (both in solution and gel form) demonstrated an advantage in reducing the wound area and inflammatory cells infiltration, improving healing rate, increasing the proliferative activity of epithelial cells and neovascularization as compared with the untreated group. Thus, the use of rhHB-EGF is a promising direction in the treatment of skin wounds.
Heparin-binding EGF-like growth factor: mechanisms of biological activity and potential therapeutic applications
L. M. Dronko1, T. M. Lutsenko1*, N. V. Korotkevych2,
I. O. Vovk2, D. A. Zhukova2, S. I. Romaniuk2,
A. A. Siromolot2, A. J. Labyntsev2, D. V. Kolybo2
1National Technical University of Ukraine “Igor Sikorsky Kyiv Polytechnic Institute”, Kyiv;
2Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: lutsenko.tetiana@lll.kpi.ua
Received: 06 August 2024; Revised: 18 September 2024;
Accepted: 07 October 2024; Available on-line: 28 October 2024
The diphtheria toxin receptor on sensitive mammalian cells is known as the membrane anchored precursor of heparin-binding EGF-like growth factor (HB-EGF). When the precursor is cleaved by metalloproteinases, a soluble form (sHB-EGF) is formed that can bind to the EGF receptors, resulting in activation of signaling pathways that regulate cell proliferation, differentiation, migration, and inhibition of apoptosis. The ability of HB-EGF to cause both positive and negative consequences for organism underscores the complexity of its biological functions and the need for a nuanced understanding of its role in health and disease. In this review the data on the HB-EGF structure, biological activity, involvement in the mechanism of diphtheria toxin action, wound healing, tumor progression as well as the methods of HB-EGF delivery are summarized.
Role of the heparin-binding domain in intracellular trafficking of sHB-EGF
O. I. Krynina, K. Yu. Manoilov, D. V. Kolybo, S. V. Komisarenko
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: olyakrynina@gmail.com
Received: 11 July 2018; Accepted: 17 May 2019
Heparin-binding EGF-like growth factor (HB-EGF) is a member of the epidermal growth factor family that was proven as a potent mitogen and chemoattractant. HB-EGF mediated EGFR activation is a key event in the stimulation of gene expression, cell migration and proliferation during both normal and pathogenic physiological processes. The main goal of this research was to reveal the role of the heparin-binding domain of HB-EGF in the ligand-receptor formation and its further internalization to the cytoplasm. We used fluorescently-labeled recombinant derivative of soluble HB-EGF and its truncated form (sHB-EGFΔ84–106) with deletion of the heparin-binding domain. Firstly, the binding kinetics of two forms of sHB-EGF to its cell surface receptors was determined using flow cytometry. To determine how the absence of heparin-binding domain in the structure of HB-EGF affects its internalization, we analyzed the endocytosis process of EGFP-sHB-EGFΔ84–106 and EGFP-sHB-EGF complexes by confocal microscopy. It was found that the full-size form of HB-EGF is characterized by a lower intensity of translocation to the cytoplasm in comparison to HBD-deleted form. Thus, differences in the trafficking of the full-size or truncated forms of sHB-EGF in the cell cytoplasm may reflect the mechanisms of extracellular matrix influence on the biological activity of sHB‑EGF.