Epidermal growth factor

Structure

In humans, EGF has 53 amino acids (sequence NSDSECPLSHDGYCLHDGVCMYIEALDKYACNCVVGYIGERCzYRDLKWWELR), with a molecular mass of around 6 kDa. It contains three disulfide bridges (Cys6-Cys20, Cys14-Cys31, Cys33-Cys42).

Function

EGF, via binding to its cognate receptor, results in cellular proliferation, differentiation, and survival.

Salivary EGF, which seems to be regulated by dietary inorganic iodine, also plays an important physiological role in the maintenance of oro-esophageal and gastric tissue integrity. The biological effects of salivary EGF include healing of oral and gastroesophageal ulcers, inhibition of gastric acid secretion, stimulation of DNA synthesis as well as mucosal protection from intraluminal injurious factors such as gastric acid, bile acids, pepsin, and trypsin and to physical, chemical and bacterial agents.

Biological sources

The Epidermal growth factor can be found in platelets, urine, saliva, milk, tears, and blood plasma. It can also be found in the submandibular glands, and the parotid gland. The production of EGF has been found to be stimulated by testosterone.

Polypeptide growth factors

Polypeptide growth factors include:

Mechanism

EGF acts by binding with high affinity to epidermal growth factor receptor (EGFR) on the cell surface. This stimulates ligand-induced dimerization, activating the intrinsic protein-tyrosine kinase activity of the receptor (see the second diagram). The tyrosine kinase activity, in turn, initiates a signal transduction cascade that results in a variety of biochemical changes within the cell – a rise in intracellular calcium levels, increased glycolysis and protein synthesis, and increases in the expression of certain genes including the gene for EGFR – that ultimately lead to DNA synthesis and cell proliferation.

EGF-family / EGF-like domain

Main article: EGF-like domain

EGF is the founding member of the EGF-family of proteins. Members of this protein family have highly similar structural and functional characteristics. Besides EGF itself other family members include:

• Heparin-binding EGF-like growth factor (HB-EGF)
• transforming growth factor-α (TGF-α)
• Amphiregulin (AR)
• Epiregulin (EPR)
• Epigen
• Betacellulin (BTC)
• neuregulin-1 (NRG1)
• neuregulin-2 (NRG2)
• neuregulin-3 (NRG3)
• neuregulin-4 (NRG4).

All family members contain one or more repeats of the conserved amino acid sequence:

CX7CX4-5CX10-13CXCX8GXRC

Where C is cysteine, G is glycine, R is arginine, and X represents any amino acid.

This sequence contains six cysteine residues that form three intramolecular disulfide bonds. Disulfide bond formation generates three structural loops that are essential for high-affinity binding between members of the EGF-family and their cell-surface receptors.

Interactions

Epidermal growth factor has been shown to interact with epidermal growth factor receptors.

Medical uses

Recombinant human epidermal growth factor, sold under the brand name Heberprot-P, is used to treat diabetic foot ulcers. It can be given by injection into the wound site, or may be used topically. Tentative evidence shows improved wound healing. Safety has been poorly studied.

EGF is used to modify synthetic scaffolds for manufacturing of bioengineered grafts by emulsion electrospinning or surface modification methods.

Bone regeneration

EGF plays an enhancer role on the osteogenic differentiation of dental pulp stem cells (DPSCs) because it is capable of increasing extracellular matrix mineralization. A low concentration of EGF (10 ng/ml) is sufficient to induce morphological and phenotypic changes. These data suggests that DPSCs in combination with EGF could be an effective stem cell-based therapy to bone tissue engineering applications in periodontics and oral implantology.

History

EGF was the second growth factor to be identified. Initially, human EGF was known as urogastrone. Stanley Cohen discovered EGF while working with Rita Levi-Montalcini at the Washington University in St. Louis during experiments researching nerve growth factor. For these discoveries Levi-Montalcini and Cohen were awarded the 1986 Nobel Prize in Physiology or Medicine.

References

References

1. (March 2003). "EGF receptor ligands". Experimental Cell Research.
2. (May 1990). "Epidermal growth factor". The Journal of Biological Chemistry.
3. (5 July 2022). "A comparative profile of total protein and six angiogenically-active growth factors in three platelet products". GMS Interdisciplinary Plastic and Reconstructive Surgery DGPW.
4. (May 1980). "Epidermal growth factor-urogastrone: biological activity and receptor binding of derivatives". Molecular Pharmacology.
5. (2004). "Review of epidermal growth factor receptor biology". International Journal of Radiation Oncology, Biology, Physics.
6. (2009). "Iodine in evolution of salivary glands and in oral health". Nutrition and Health.
7. (2005). "Robbins and Cotran pathologic basis of disease". Elsevier Saunders.
8. (2013-01-01). "Chapter 624 - Mouse Kallikrein 9, Epidermal Growth Factor-binding Protein". Academic Press.
9. (2002). "Biochemistry". Books and Allied.
10. (September 2005). "Epidermal growth factor receptor dimerization and activation require ligand-induced conformational changes in the dimer interface". Molecular and Cellular Biology.
11. (June 1984). "Epidermal growth factor immunoreactive material in the central nervous system: location and development". Science.
12. (May 2006). "The epidermal growth factor receptors and their family of ligands: their putative role in atherogenesis". Atherosclerosis.
13. (July 2002). "Role of the N-terminus of epidermal growth factor in ErbB-2/ErbB-3 binding studied by phage display". Biochemistry.
14. (March 1999). "A differential requirement for the COOH-terminal region of the epidermal growth factor (EGF) receptor in amphiregulin and EGF mitogenic signaling". The Journal of Biological Chemistry.
15. (January 2013). "Heberprot-P: a novel product for treating advanced diabetic foot ulcer". MEDICC Review.
16. (June 2016). "Efficacy of Topical Recombinant Human Epidermal Growth Factor for Treatment of Diabetic Foot Ulcer: A Systematic Review and Meta-Analysis". The International Journal of Lower Extremity Wounds.
17. (October 2015). "Growth factors for treating diabetic foot ulcers". The Cochrane Database of Systematic Reviews.
18. (January 2016). "Fabrication and surface modification of poly lactic acid (PLA) scaffolds with epidermal growth factor for neural tissue engineering". Biomatter.
19. (2017). "Modification of biodegradable fibrous scaffolds with Epidermal Growth Factor by emulsion electrospinning for promotion of epithelial cells proliferation". Гены и клетки.
20. (September 2015). "Epidermal growth factor enhances osteogenic differentiation of dental pulp stem cells in vitro". Head & Face Medicine.
21. (2006-01-01). "Encyclopedia of Respiratory Medicine". Academic Press.