Epidermal growth factor: Difference between revisions

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(Submandibular and submaxillary refer to the same thing. Submaxillary is a historical term.)
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{{Distinguish|EF-G}}
{{Distinguish|EF-G}}
{{Infobox_gene}}
{{Infobox_gene}}
'''Epidermal growth factor''' ('''EGF''') stimulates [[cell growth]] and [[Cellular differentiation|differentiation]] by binding to its receptor, [[Epidermal growth factor receptor|EGFR]]. Human EGF is a 6-k[[dalton (unit)|Da]] [[protein]]<ref name="pmid12648462">{{cite journal| vauthors = Harris RC, Chung E, Coffey RJ| title = EGF receptor ligands| journal = Experimental Cell Research| volume = 284| issue = 1| pages = 2–13| date = March 2003| pmid = 12648462| doi = 10.1016/S0014-4827(02)00105-2}}</ref> with 53 [[amino acid|amino acid residues]] and three intramolecular [[disulfide bond]]s.<ref name="pmid2186024">{{cite journal| vauthors = Carpenter G, Cohen S| title = Epidermal growth factor| journal = The Journal of Biological Chemistry| volume = 265| issue = 14| pages = 7709–12| date = May 1990| pmid = 2186024| doi = |url = http://www.jbc.org/cgi/reprint/265/14/7709}}</ref>
'''Epidermal growth factor''' ('''EGF''') stimulates [[cell growth]] and [[Cellular differentiation|differentiation]] by binding to its receptor, [[Epidermal growth factor receptor|EGFR]]. Human EGF is a 6-k[[dalton (unit)|Da]] [[protein]]<ref name="pmid12648462">{{cite journal | vauthors = Harris RC, Chung E, Coffey RJ | title = EGF receptor ligands | journal = Experimental Cell Research | volume = 284 | issue = 1 | pages = 2–13 | date = March 2003 | pmid = 12648462 | doi = 10.1016/S0014-4827(02)00105-2 }}</ref> with 53 [[amino acid|amino acid residues]] and three intramolecular [[disulfide bond]]s.<ref name="pmid2186024">{{cite journal | vauthors = Carpenter G, Cohen S | title = Epidermal growth factor | journal = The Journal of Biological Chemistry | volume = 265 | issue = 14 | pages = 7709–12 | date = May 1990 | pmid = 2186024 | doi = | url = http://www.jbc.org/cgi/reprint/265/14/7709 }}</ref>


EGF was originally described as a secreted peptide found in the [[submaxillary gland]]s of [[Mus musculus|mice]] and in human [[urine]]. EGF has since been found in many human tissues including submandibular gland, parotid gland.<ref name=Venturi2009/>  Initially, human EGF was known as '''urogastrone'''.<ref>{{cite journal|last1=Hollenberg|first1=MD|last2=Gregory|first2=H|title=Epidermal growth factor-urogastrone: biological activity and receptor binding of derivatives.|journal=Molecular Pharmacology|date=May 1980|volume=17|issue=3|pages=314–20|pmid=6248761|url=http://molpharm.aspetjournals.org/content/17/3/314}}</ref>
EGF was originally described as a secreted peptide found in the [[submaxillary gland]]s of [[Mus musculus|mice]] and in human [[urine]]. EGF has since been found in many human tissues including [[submandibular gland]] (submaxillary gland) and [[parotid gland]].<ref name=Venturi2009/>  Initially, human EGF was known as '''urogastrone'''.<ref>{{cite journal | vauthors = Hollenberg MD, Gregory H | title = Epidermal growth factor-urogastrone: biological activity and receptor binding of derivatives | journal = Molecular Pharmacology | volume = 17 | issue = 3 | pages = 314–20 | date = May 1980 | pmid = 6248761 | url = http://molpharm.aspetjournals.org/content/17/3/314 }}</ref>


== Function ==
== Function ==
EGF [binding to EGFR] results in cellular proliferation, differentiation, and survival.<ref name="Herbst">{{cite journal | author = Herbst RS | title = Review of epidermal growth factor receptor biology | journal = International Journal of Radiation Oncology, Biology, Physics | volume = 59 | issue = 2 Suppl | pages = 21–6 | year = 2004 | pmid = 15142631 | doi = 10.1016/j.ijrobp.2003.11.041 }}</ref>
EGF [binding to EGFR] results in cellular proliferation, differentiation, and survival.<ref name="Herbst">{{cite journal | vauthors = Herbst RS | title = Review of epidermal growth factor receptor biology | journal = International Journal of Radiation Oncology, Biology, Physics | volume = 59 | issue = 2 Suppl | pages = 21–6 | year = 2004 | pmid = 15142631 | doi = 10.1016/j.ijrobp.2003.11.041 }}</ref>


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.<ref name=Venturi2009>{{cite journal | vauthors = Venturi S, Venturi M | title = Iodine in evolution of salivary glands and in oral health | journal = Nutrition and Health | volume = 20 | issue = 2 | pages = 119–134 | year = 2009 | pmid = 19835108 | doi = 10.1177/026010600902000204 }}</ref>
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.<ref name=Venturi2009>{{cite journal | vauthors = Venturi S, Venturi M | title = Iodine in evolution of salivary glands and in oral health | journal = Nutrition and Health | volume = 20 | issue = 2 | pages = 119–34 | year = 2009 | pmid = 19835108 | doi = 10.1177/026010600902000204 }}</ref>


== Biological sources ==
== Biological sources ==
Epidermal growth factor can be found in urine, saliva, milk, and plasma.<ref name="isbn0-7216-0187-1">{{cite book | author = Cotran, Ramzi S. | author2 = Kumar, Vinay | author3 = Fausto, Nelson | author4 = Nelso Fausto | author5 = Robbins, Stanley L. | author6 = Abbas, Abul K. | others = | title = Robbins and Cotran pathologic basis of disease | edition = | language = | publisher = Elsevier Saunders | location = St. Louis, Mo | year = 2005 | isbn = 0-7216-0187-1 }}</ref>
Epidermal growth factor can be found in urine, saliva, milk, and plasma.<ref name="isbn0-7216-0187-1">{{cite book | first1 = Vinay | last1 = Kumar | first2 = Abul K | last2 = Abbas | first3 = Nelson | last3 = Fausto | first4 = Stanley L | last4 = Robbins | first5 = Ramzi S | last5 = Cotran | name-list-format = vanc  | title = Robbins and Cotran pathologic basis of disease | edition = 7th | publisher = Elsevier Saunders | location = St. Louis, Mo | year = 2005 | isbn = 978-0-7216-0187-8 }}</ref>
The production of epidermal growth factor has been found to be stimulated by testosterone.
The production of epidermal growth factor has been found to be stimulated by testosterone.


== Mechanism ==
== Mechanism ==
[[File:MAPKpathway diagram.svg|thumb|left|Diagram showing key components of the [[MAPK/ERK pathway]]. In the diagram, "P" represents  [[phosphate]]. Note EGF at the very top.]]
[[File:MAPKpathway diagram.svg|thumb|left|Diagram showing key components of the [[MAPK/ERK pathway]]. In the diagram, "P" represents  [[phosphate]]. Note EGF at the very top.]]
EGF acts by binding with high [[Affinity (pharmacology)|affinity]] to [[epidermal growth factor receptor]] (EGFR) on the [[plasma membrane|cell surface]]. This stimulates ligand-induced dimerization,<ref name="pmid16107719">{{cite journal | vauthors = Dawson JP, Berger MB, Lin CC, Schlessinger J, Lemmon MA, Ferguson KM | title = Epidermal growth factor receptor dimerization and activation require ligand-induced conformational changes in the dimer interface | journal = Mol. Cell. Biol. | volume = 25 | issue = 17 | pages = 7734–42 | year = 2005 | pmid = 16107719 | pmc = 1190273 | doi = 10.1128/MCB.25.17.7734-7742.2005 }}</ref> 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 [[biochemistry|biochemical]] changes within the cell – a rise in intracellular [[calcium]] levels, increased [[glycolysis]] and [[protein synthesis]], and increases in the [[gene expression|expression]] of certain [[gene]]s including the gene for EGFR – that ultimately lead to [[DNA replication|DNA synthesis]] and cell proliferation.<ref name="pmid6144184">{{cite journal | vauthors = Fallon JH, Seroogy KB, Loughlin SE, Morrison RS, Bradshaw RA, Knaver DJ, Cunningham DD | title = Epidermal growth factor immunoreactive material in the central nervous system: location and development | journal = Science | volume = 224 | issue = 4653 | pages = 1107–9 | date = June 1984 | pmid = 6144184 | doi = 10.1126/science.6144184 }}</ref>
EGF acts by binding with high [[Affinity (pharmacology)|affinity]] to [[epidermal growth factor receptor]] (EGFR) on the [[plasma membrane|cell surface]]. This stimulates ligand-induced dimerization,<ref name="pmid16107719">{{cite journal | vauthors = Dawson JP, Berger MB, Lin CC, Schlessinger J, Lemmon MA, Ferguson KM | title = Epidermal growth factor receptor dimerization and activation require ligand-induced conformational changes in the dimer interface | journal = Molecular and Cellular Biology | volume = 25 | issue = 17 | pages = 7734–42 | date = September 2005 | pmid = 16107719 | pmc = 1190273 | doi = 10.1128/MCB.25.17.7734-7742.2005 }}</ref> 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 [[biochemistry|biochemical]] changes within the cell – a rise in intracellular [[calcium]] levels, increased [[glycolysis]] and [[protein synthesis]], and increases in the [[gene expression|expression]] of certain [[gene]]s including the gene for EGFR – that ultimately lead to [[DNA replication|DNA synthesis]] and cell proliferation.<ref name="pmid6144184">{{cite journal | vauthors = Fallon JH, Seroogy KB, Loughlin SE, Morrison RS, Bradshaw RA, Knaver DJ, Cunningham DD | title = Epidermal growth factor immunoreactive material in the central nervous system: location and development | journal = Science | volume = 224 | issue = 4653 | pages = 1107–9 | date = June 1984 | pmid = 6144184 | doi = 10.1126/science.6144184 }}</ref>


== EGF-family / EGF-like domain ==
== EGF-family / EGF-like domain ==
EGF is the founding member of the [[EGF-like domain|EGF-family of proteins]]. Members of this protein family have highly similar structural and functional characteristics. Besides EGF itself other family members include:<ref name="dreux">{{cite journal | vauthors = Dreux AC, Lamb DJ, Modjtahedi H, Ferns GA | title = The epidermal growth factor receptors and their family of ligands: their putative role in atherogenesis | journal = Atherosclerosis | volume = 186 | issue = 1 | pages = 38–53 | date = May 2006 | pmid = 16076471 | doi = 10.1016/j.atherosclerosis.2005.06.038}}</ref>
EGF is the founding member of the [[EGF-like domain|EGF-family of proteins]]. Members of this protein family have highly similar structural and functional characteristics. Besides EGF itself other family members include:<ref name="dreux">{{cite journal | vauthors = Dreux AC, Lamb DJ, Modjtahedi H, Ferns GA | title = The epidermal growth factor receptors and their family of ligands: their putative role in atherogenesis | journal = Atherosclerosis | volume = 186 | issue = 1 | pages = 38–53 | date = May 2006 | pmid = 16076471 | doi = 10.1016/j.atherosclerosis.2005.06.038 }}</ref>
*[[Heparin-binding EGF-like growth factor]] (HB-EGF)
*[[Heparin-binding EGF-like growth factor]] (HB-EGF)
*[[TGF alpha|transforming growth factor-α]] (TGF-α)
*[[TGF alpha|transforming growth factor-α]] (TGF-α)
Line 37: Line 37:
Where '''X''' represents any [[amino acid]].<ref name=dreux/>
Where '''X''' represents any [[amino acid]].<ref name=dreux/>


This sequence contains 6 [[cysteine]] residues that form three intramolecular [[disulfide bond]]s. 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.<ref name=harris>{{cite journal | vauthors = Harris RC, Chung E, Coffey RJ | title = EGF receptor ligands | journal = Exp. Cell Res. | volume = 284 | issue = 1 | pages = 2–13 | year = 2003 | pmid = 12648462 | doi = 10.1016/S0014-4827(02)00105-2 }}</ref>
This sequence contains 6 [[cysteine]] residues that form three intramolecular [[disulfide bond]]s. 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.<ref name=harris>{{cite journal | vauthors = Harris RC, Chung E, Coffey RJ | title = EGF receptor ligands | journal = Experimental Cell Research | volume = 284 | issue = 1 | pages = 2–13 | date = March 2003 | pmid = 12648462 | doi = 10.1016/S0014-4827(02)00105-2 }}</ref>


==Interactions==
== Interactions ==
Epidermal growth factor has been shown to [[Protein-protein interaction|interact]] with [[epidermal growth factor receptor]].<ref name="pmid12093292">{{cite journal | vauthors = Stortelers C, Souriau C, van Liempt E, van de Poll ML, van Zoelen EJ | title = Role of the N-terminus of epidermal growth factor in ErbB-2/ErbB-3 binding studied by phage display | journal = Biochemistry | volume = 41 | issue = 27 | pages = 8732–41 | date = July 2002 | pmid = 12093292 | doi = 10.1021/bi025878c }}</ref><ref name="pmid10085134">{{cite journal | vauthors = Wong L, Deb TB, Thompson SA, Wells A, Johnson GR | title = A differential requirement for the COOH-terminal region of the epidermal growth factor (EGF) receptor in amphiregulin and EGF mitogenic signaling | journal = J. Biol. Chem. | volume = 274 | issue = 13 | pages = 8900–9 | date = March 1999 | pmid = 10085134 | doi = 10.1074/jbc.274.13.8900 }}</ref>
 
Epidermal growth factor has been shown to [[Protein-protein interaction|interact]] with [[epidermal growth factor receptor]].<ref name="pmid12093292">{{cite journal | vauthors = Stortelers C, Souriau C, van Liempt E, van de Poll ML, van Zoelen EJ | title = Role of the N-terminus of epidermal growth factor in ErbB-2/ErbB-3 binding studied by phage display | journal = Biochemistry | volume = 41 | issue = 27 | pages = 8732–41 | date = July 2002 | pmid = 12093292 | doi = 10.1021/bi025878c }}</ref><ref name="pmid10085134">{{cite journal | vauthors = Wong L, Deb TB, Thompson SA, Wells A, Johnson GR | title = A differential requirement for the COOH-terminal region of the epidermal growth factor (EGF) receptor in amphiregulin and EGF mitogenic signaling | journal = The Journal of Biological Chemistry | volume = 274 | issue = 13 | pages = 8900–9 | date = March 1999 | pmid = 10085134 | doi = 10.1074/jbc.274.13.8900 }}</ref>


==Medical uses==
==Medical uses==
[[Recombinant protein|Recombinant]] human epidermal growth factor, sold under the brand name Heberprot-P, is used to treat [[diabetic foot ulcer]]s. It can be given by injection into the wound site,<ref name=Ber2013>{{cite journal |title=Heberprot-P: a novel product for treating advanced diabetic foot ulcer |last=Berlanga |first=J. |last2=Fernández |first2=J. I. |last3=López |first3=E. |last4=López |first4=P. A. |last5=del Río |first5=A. |last6=Valenzuela |first6=C. |last7=Baldomero |first7=J. |last8=Muzio |first8=V. |last9=Raíces |first9=M. |last10=Silva |first10=R. |last11=Acevedo |first11=B. E. |last12=Herrera |first12=L. |journal=[[MEDICC|MEDICC Review]] |year=2013 |volume=15 |issue=1 |pages=11–15 |pmid=23396236 |doi=10.1590/s1555-79602013000100004}}</ref> or may be used topically.<ref>{{cite journal|last1=Yang|first1=S|last2=Geng|first2=Z|last3=Ma|first3=K|last4=Sun|first4=X|last5=Fu|first5=X|title=Efficacy of Topical Recombinant Human Epidermal Growth Factor for Treatment of Diabetic Foot Ulcer: A Systematic Review and Meta-Analysis.|journal=The International Journal of Lower Extremity Wounds|date=June 2016|volume=15|issue=2|pages=120–5|pmid=27151755|doi=10.1177/1534734616645444}}</ref> Tentative evidence shows improved wound healing.<ref name=Mar2015>{{cite journal|last1=Martí-Carvajal|first1=AJ|last2=Gluud|first2=C|last3=Nicola|first3=S|last4=Simancas-Racines|first4=D|last5=Reveiz|first5=L|last6=Oliva|first6=P|last7=Cedeño-Taborda|first7=J|title=Growth factors for treating diabetic foot ulcers.|journal=The Cochrane Database of Systematic Reviews|date=28 October 2015|volume=10|pages=CD008548|pmid=26509249|doi=10.1002/14651858.CD008548.pub2}}</ref> Safety has been poorly studied.<ref name=Mar2015/>
[[Recombinant protein|Recombinant]] human epidermal growth factor, sold under the brand name Heberprot-P, is used to treat [[diabetic foot ulcer]]s. It can be given by injection into the wound site,<ref name=Ber2013>{{cite journal | vauthors = Berlanga J, Fernández JI, López E, López PA, del Río A, Valenzuela C, Baldomero J, Muzio V, Raíces M, Silva R, Acevedo BE, Herrera L | title = Heberprot-P: a novel product for treating advanced diabetic foot ulcer | journal = MEDICC Review | volume = 15 | issue = 1 | pages = 11–5 | date = January 2013 | pmid = 23396236 | doi = 10.1590/s1555-79602013000100004 }}</ref> or may be used topically.<ref>{{cite journal | vauthors = Yang S, Geng Z, Ma K, Sun X, Fu X | title = Efficacy of Topical Recombinant Human Epidermal Growth Factor for Treatment of Diabetic Foot Ulcer: A Systematic Review and Meta-Analysis | journal = The International Journal of Lower Extremity Wounds | volume = 15 | issue = 2 | pages = 120–5 | date = June 2016 | pmid = 27151755 | doi = 10.1177/1534734616645444 }}</ref> Tentative evidence shows improved wound healing.<ref name=Mar2015>{{cite journal | vauthors = Martí-Carvajal AJ, Gluud C, Nicola S, Simancas-Racines D, Reveiz L, Oliva P, Cedeño-Taborda J | title = Growth factors for treating diabetic foot ulcers | journal = The Cochrane Database of Systematic Reviews | volume = 10 | issue = 10 | pages = CD008548 | date = October 2015 | pmid = 26509249 | doi = 10.1002/14651858.CD008548.pub2 }}</ref> Safety has been poorly studied.<ref name=Mar2015/>
 
EGF is used to modify synthetic scaffolds for manufacturing of [[Biological engineering|bioengineered]] grafts by emulsion [[electrospinning]] or surface modification methods.<ref>{{cite journal | vauthors = Haddad T, Noel S, Liberelle B, El Ayoubi R, Ajji A, De Crescenzo G | title = Fabrication and surface modification of poly lactic acid (PLA) scaffolds with epidermal growth factor for neural tissue engineering | journal = Biomatter | volume = 6 | issue = 1 | pages = e1231276 | date = January 2016 | pmid = 27740881 | pmc = 5098722 | doi = 10.1080/21592535.2016.1231276 }}</ref><ref>{{Cite journal|last=Tenchurin|first=T.H.|last2=Lyundup|first2=A.V.|last3=Demchenko|first3=A.G.|last4=Krasheninnikov|first4=M.E.|last5=Balyasin|first5=M.V.|last6=Klabukov|first6=I.D.|last7=Shepelev|first7=A.D.|last8=Mamagulashvili|first8=V.G.|last9=Orehov|first9=A.S.|date=2017|title=Modification of biodegradable fibrous scaffolds with Epidermal Growth Factor by emulsion electrospinning for promotion of epithelial cells proliferation|url=https://zenodo.org/record/1175806|journal=Гены и клетки / Geny i kletki / Genes and Cells |language=ru|volume=12|issue=4|pages=47–52|doi=10.23868/201707029|via=}}</ref>
 
== Bone regeneration ==
EGF plays an enhancer role on 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|oral implantology]].<ref>{{cite journal | vauthors = Del Angel-Mosqueda C, Gutiérrez-Puente Y, López-Lozano AP, Romero-Zavaleta RE, Mendiola-Jiménez A, Medina-De la Garza CE, Márquez-M M, De la Garza-Ramos MA | title = Epidermal growth factor enhances osteogenic differentiation of dental pulp stem cells in vitro | journal = Head & Face Medicine | volume = 11 | pages = 29 | date = September 2015 | pmid = 26334535 | doi = 10.1186/s13005-015-0086-5 | url = https://doi.org/10.1186/s13005-015-0086-5 }}</ref>


== References ==
== References ==
Line 50: Line 56:
== Further reading ==
== Further reading ==
{{refbegin|35em}}
{{refbegin|35em}}
*{{cite journal | vauthors = Boonstra J, Rijken P, Humbel B, Cremers F, Verkleij A, van Bergen en Henegouwen P | title = The epidermal growth factor | journal = Cell Biol. Int. | volume = 19 | issue = 5 | pages = 413–30 | year = 1995 | pmid = 7640657 | doi = 10.1006/cbir.1995.1086 }}
* {{cite journal | vauthors = Boonstra J, Rijken P, Humbel B, Cremers F, Verkleij A, van Bergen en Henegouwen P | title = The epidermal growth factor | journal = Cell Biology International | volume = 19 | issue = 5 | pages = 413–30 | date = May 1995 | pmid = 7640657 | doi = 10.1006/cbir.1995.1086 }}
*{{cite journal | author = Dvorak B | title = Epidermal growth factor and necrotizing enterocolitis | journal = Clinics in Perinatology | volume = 31 | issue = 1 | pages = 183–92 | year = 2004 | pmid = 15183666 | doi = 10.1016/j.clp.2004.03.015 }}
* {{cite journal | vauthors = Dvorak B | title = Epidermal growth factor and necrotizing enterocolitis | journal = Clinics in Perinatology | volume = 31 | issue = 1 | pages = 183–92 | date = March 2004 | pmid = 15183666 | doi = 10.1016/j.clp.2004.03.015 }}
*{{cite journal | author = Howell WM | title = Epidermal growth factor gene polymorphism and development of cutaneous melanoma | journal = J. Invest. Dermatol. | volume = 123 | issue = 4 | pages = xx–xxi | year = 2004 | pmid = 15373802 | doi = 10.1111/j.0022-202X.2004.23308.x }}
* {{cite journal | vauthors = Howell WM | title = Epidermal growth factor gene polymorphism and development of cutaneous melanoma | journal = The Journal of Investigative Dermatology | volume = 123 | issue = 4 | pages = xx-xxi | date = October 2004 | pmid = 15373802 | doi = 10.1111/j.0022-202X.2004.23308.x }}
{{refend}}
{{refend}}


Revision as of 01:10, 4 June 2018

Not to be confused with EF-G.
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Epidermal growth factor (EGF) stimulates cell growth and differentiation by binding to its receptor, EGFR. Human EGF is a 6-kDa protein[1] with 53 amino acid residues and three intramolecular disulfide bonds.[2]

EGF was originally described as a secreted peptide found in the submaxillary glands of mice and in human urine. EGF has since been found in many human tissues including submandibular gland (submaxillary gland) and parotid gland.[3] Initially, human EGF was known as urogastrone.[4]

Function

EGF [binding to EGFR] results in cellular proliferation, differentiation, and survival.[5]

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.[3]

Biological sources

Epidermal growth factor can be found in urine, saliva, milk, and plasma.[6] The production of epidermal growth factor has been found to be stimulated by testosterone.

Mechanism

File:MAPKpathway diagram.svg
Diagram showing key components of the MAPK/ERK pathway. In the diagram, "P" represents phosphate. Note EGF at the very top.

EGF acts by binding with high affinity to epidermal growth factor receptor (EGFR) on the cell surface. This stimulates ligand-induced dimerization,[7] 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.[8]

EGF-family / 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:[9]

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

CX7CX4-5CX10-13CXCX8GXRC

Where X represents any amino acid.[9]

This sequence contains 6 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.[10]

Interactions

Epidermal growth factor has been shown to interact with epidermal growth factor receptor.[11][12]

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,[13] or may be used topically.[14] Tentative evidence shows improved wound healing.[15] Safety has been poorly studied.[15]

EGF is used to modify synthetic scaffolds for manufacturing of bioengineered grafts by emulsion electrospinning or surface modification methods.[16][17]

Bone regeneration

EGF plays an enhancer role on 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.[18]

References

  1. ↑ Harris RC, Chung E, Coffey RJ (March 2003). "EGF receptor ligands". Experimental Cell Research. 284 (1): 2–13. doi:10.1016/S0014-4827(02)00105-2. PMID 12648462.
  2. ↑ Carpenter G, Cohen S (May 1990). "Epidermal growth factor". The Journal of Biological Chemistry. 265 (14): 7709–12. PMID 2186024.
  3. ↑ 3.0 3.1 Venturi S, Venturi M (2009). "Iodine in evolution of salivary glands and in oral health". Nutrition and Health. 20 (2): 119–34. doi:10.1177/026010600902000204. PMID 19835108.
  4. ↑ Hollenberg MD, Gregory H (May 1980). "Epidermal growth factor-urogastrone: biological activity and receptor binding of derivatives". Molecular Pharmacology. 17 (3): 314–20. PMID 6248761.
  5. ↑ Herbst RS (2004). "Review of epidermal growth factor receptor biology". International Journal of Radiation Oncology, Biology, Physics. 59 (2 Suppl): 21–6. doi:10.1016/j.ijrobp.2003.11.041. PMID 15142631.
  6. ↑ Kumar V, Abbas AK, Fausto N, Robbins SL, Cotran RS (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. ISBN 978-0-7216-0187-8.
  7. ↑ Dawson JP, Berger MB, Lin CC, Schlessinger J, Lemmon MA, Ferguson KM (September 2005). "Epidermal growth factor receptor dimerization and activation require ligand-induced conformational changes in the dimer interface". Molecular and Cellular Biology. 25 (17): 7734–42. doi:10.1128/MCB.25.17.7734-7742.2005. PMC 1190273. PMID 16107719.
  8. ↑ Fallon JH, Seroogy KB, Loughlin SE, Morrison RS, Bradshaw RA, Knaver DJ, Cunningham DD (June 1984). "Epidermal growth factor immunoreactive material in the central nervous system: location and development". Science. 224 (4653): 1107–9. doi:10.1126/science.6144184. PMID 6144184.
  9. ↑ 9.0 9.1 Dreux AC, Lamb DJ, Modjtahedi H, Ferns GA (May 2006). "The epidermal growth factor receptors and their family of ligands: their putative role in atherogenesis". Atherosclerosis. 186 (1): 38–53. doi:10.1016/j.atherosclerosis.2005.06.038. PMID 16076471.
  10. ↑ Harris RC, Chung E, Coffey RJ (March 2003). "EGF receptor ligands". Experimental Cell Research. 284 (1): 2–13. doi:10.1016/S0014-4827(02)00105-2. PMID 12648462.
  11. ↑ Stortelers C, Souriau C, van Liempt E, van de Poll ML, van Zoelen EJ (July 2002). "Role of the N-terminus of epidermal growth factor in ErbB-2/ErbB-3 binding studied by phage display". Biochemistry. 41 (27): 8732–41. doi:10.1021/bi025878c. PMID 12093292.
  12. ↑ Wong L, Deb TB, Thompson SA, Wells A, Johnson GR (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. 274 (13): 8900–9. doi:10.1074/jbc.274.13.8900. PMID 10085134.
  13. ↑ Berlanga J, Fernández JI, López E, López PA, del Río A, Valenzuela C, Baldomero J, Muzio V, Raíces M, Silva R, Acevedo BE, Herrera L (January 2013). "Heberprot-P: a novel product for treating advanced diabetic foot ulcer". MEDICC Review. 15 (1): 11–5. doi:10.1590/s1555-79602013000100004. PMID 23396236.
  14. ↑ Yang S, Geng Z, Ma K, Sun X, Fu X (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. 15 (2): 120–5. doi:10.1177/1534734616645444. PMID 27151755.
  15. ↑ 15.0 15.1 Martí-Carvajal AJ, Gluud C, Nicola S, Simancas-Racines D, Reveiz L, Oliva P, Cedeño-Taborda J (October 2015). "Growth factors for treating diabetic foot ulcers". The Cochrane Database of Systematic Reviews. 10 (10): CD008548. doi:10.1002/14651858.CD008548.pub2. PMID 26509249.
  16. ↑ Haddad T, Noel S, Liberelle B, El Ayoubi R, Ajji A, De Crescenzo G (January 2016). "Fabrication and surface modification of poly lactic acid (PLA) scaffolds with epidermal growth factor for neural tissue engineering". Biomatter. 6 (1): e1231276. doi:10.1080/21592535.2016.1231276. PMC 5098722. PMID 27740881.
  17. ↑ Tenchurin, T.H.; Lyundup, A.V.; Demchenko, A.G.; Krasheninnikov, M.E.; Balyasin, M.V.; Klabukov, I.D.; Shepelev, A.D.; Mamagulashvili, V.G.; Orehov, A.S. (2017). "Modification of biodegradable fibrous scaffolds with Epidermal Growth Factor by emulsion electrospinning for promotion of epithelial cells proliferation". Гены и клетки / Geny i kletki / Genes and Cells (in русский). 12 (4): 47–52. doi:10.23868/201707029.
  18. ↑ Del Angel-Mosqueda C, Gutiérrez-Puente Y, López-Lozano AP, Romero-Zavaleta RE, Mendiola-Jiménez A, Medina-De la Garza CE, Márquez-M M, De la Garza-Ramos MA (September 2015). "Epidermal growth factor enhances osteogenic differentiation of dental pulp stem cells in vitro". Head & Face Medicine. 11: 29. doi:10.1186/s13005-015-0086-5. PMID 26334535.

Further reading

External links

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