Epidermal Büyüme Faktörü

Year 2016, Volume: 9 Issue: 3, 215 - 225, 01.09.2016

Gül Fatma Yarım Filiz Kazak

Abstract

Epidermal büyüme faktörü, hücrelerin bölünmesi, farklılaşması, yaşaması, çoğalması, büyümesi ve hücre göçünü uyaran protein yapıda bir büyüme faktörü olup, organizmadaki pek çok fizyolojik ve patolojik süreçte rol almaktadır. EGF, anti-enflamatuar, anti-apoptotik, nörotrofik ve nöroprotektif etkilere sahiptir. Epidermal büyüme faktörü reseptörleri akciğer, mide, duodenum, pankreas, böbrek, hipofiz bezi, tiroid bezi, meme bezi, yumurtalık, uterus, plasenta, kornea ve gliya hücrelerinde bulunmaktadır. Trombositler, makrofajlar, monositler ve fibroblastlar da epidermal büyüme faktörü kaynağıdır. Epidermal büyüme faktörü, epidermal büyüme faktörü reseptörüne bağlanarak, MAPK, ERK 1/2, PI3K-Akt, PLC-γ, JAK/STAT hücre içi sinyalizasyon yolaklarını aktive ederek etki etmektedir. Epidermal büyüme faktörü etkilerini başlıca sindirim sistemi, üreme sistemi ve sinir sistemi üzerinde göstermektedir. Fibroblastların, kerotinisitlerin, vasküler endotel hücrelerinin büyümesini ve çoğalmasını uyarıcı etkisi nedeniyle, özellikle yaraların tedavisinde epidermal büyüme faktörü uygulamaları başarı sağlamaktadır. Bu derlemenin amacı, EGF’nin yapısı, kaynakları, reseptörü, etki mekanizması, etkileri ve tedavide kullanımını özetlemektir.

Keywords

Epidermal Büyüme Faktörü, Epidermal Büyüme Faktörü Reseptörü

Epidermal Growth Factor

Abstract

Epidermal growth factor is a growth factor in protein structure that stimulating division, differentiation, survival, proliferation, growth and migration of the cells which takes role in many physiological and pathological processes of the organism. EGF has anti-inflammatory, anti-apoptotic, neuroprotective and neurotrophic effects. Epidermal growth factor receptors are located on the cell surface of many tissues that include lung, stomach, duodenum, pancreas, kidney, pituitary gland, thyroid gland, mammary gland, ovary, uterus, placenta, cornea and glia. Platelets, macrophages, monocytes and fibroblasts are also source of epidermal growth factor. EGF exerts its effects through binding to EGFR mainly by activating MAPK, ERK 1/2, PI3K-Akt, PLC-γ, JAK/STAT intracellular signaling pathways. Epidermal growth factor exerts its effect mainly on the digestive, reproductive and nervous system. Epidermal growth factor administration especially in treatment of wounds has success because of its stimulating effect on growth and proliferation of fibroblasts, keratinocytes and vascular endothelial cells. The aim of this review is to summarize the structure, sources, receptor, effect mechanism, effects and for use in therapy of epidermal growth factor.

Keywords

Epidermal Growth Factor, Epidermal Growth Factor Receptor

References

• Acosta JB, Savigne W, Valdez C, Franco N, Alba JS, del Rio A, López-Saura P, Guillén G, Lopez E, Herrera L, Férnandez-Montequín J. Epidermal growth factor intralesional infiltrations can prevent amputation in patients with advanced diabetic foot wounds. Int Wound J. 2006; 3(3):232-239.
• Aflalo ED, Sod-Moriah UA, Potashnik G, Har-Vardi I. EGF increases expression and activity of PAs in preimplantation rat embryos and their implantation rate. Reprod Biol Endocrinol. 2007; 5:4.
• Aguirre A, Dupree JL, Mangin JM, Gallo V. A functional role for EGFR signaling in myelination and remyelination. Nat Neurosci. 2007; 10(8):990-1002.
• Altschuler LR, Parisi MN, Cageao LF, Chiocchio SR, Fernandez-Pol JA, Zaninovich AA. Epidermal growth factor stimulates thyrotropin secretion in the rat. Neuroendocrinology. 1993; 57(1):23-27.
• Aral İL, Güngör N, Oygür T, Cinel L. Epidermal Büyüme Faktörünün (EGF) Deri Allogreftleri Üzerine Olan Etkilerinin Histopatolojik olarak Araştırılması. GÜ Dişhek Fak Der. 1995; 12(1):47-53.
• Babül A, Gönül B, Özoğul C, Dinçer S, Erdoğan D, Pınar L, Çelebi N. EGF Accelerates Mice Skin Wound Healing, Proceed. 8thinler. Pharm. Technol. 1996; Symp. (IPTS-96), Sept. 9:1 Ankara-TURKEY.
• Bruder ED, Hoof JV, Young JB, Raff H. Epidermal growth factor and parathyroid hormone-related peptide mRNA in the mammary gland and their concentrations in milk: effects of postpartum hypoxia in lactating rats. Horm Metab Res. 2008; 40(7):446-453.
• Buret A, Olson ME, Gall DG, Hardin JA. Effects of orally administered epidermal growth factor on enteropathogenic Escherichia coli infection in rabbits. Infect Immun. 1998; 66(10):4917-4923.
• Burling K, Seguin MA, Marsh P, Brinkman K, Madigan J, Thurmond M, Moon-Massat P, Mannis M, Murphy CJ. Effect of topical administration of epidermal growth factor on healing of corneal epithelial defects in horses. Am J Vet Res. 2000; 61(9):1150-1155.
• Caballero ME, Calunga J, Barber E, Cruz E, López-Saura P, Boix E, Berlanga J. Epidermal growth factor-mediated prevention of renal ischemia/reperfusion injury. Biotecnol Apl. 2000; 17:161-165.
• Carpenter G, Cohen S. Human epidermal growth factor and the proliferation of human fibroblasts. J Cell Physiol. 1976; 88(2):227-237. Carpenter G. Receptors for epidermal growth factor and other polypeptide mitogens. Annu Rev Biochem. 1987; 56:881-914.
• Carpenter G, Cohen S. Epidermal Growth Factor. Ann Rev Biochem. 1979; 68:194-216.
• Chabot JG, St-Arnaud R, Walker P, Pelletier G. Distribution of epidermal growth factor receptors in the rat ovary. Mol Cell Endocrinol. 1986a; 44(2):99-108.
• Chabot JG, Walker P, Pelletier G. Distribution of epidermal growth factor binding sites in the adult rat anterior pituitary gland. Peptides. 1986b; 7(1):45-50.
• Chandra A, Lan S, Zhu J, Siclari VA, Qin L. Epidermal growth factor receptor (EGFR) signaling promotes proliferation and survival in osteoprogenitors by increasing early growth response 2 (EGR2) expression. J Biol Chem. 2013; 288(28):20488-20498.
• Chegini N, Rao CV, Wakim N, Sanfilippo J. Binding of 125I-epidermal growth factor in human uterus. Cell Tissue Res. 1986; 246(3):543-548.
• Childs GV, Patterson J, Unabia G, Rougeau D, Wu P. Epidermal growth factor enhances ACTH secretion and expression of POMC mRNA by corticotropes in mixed and enriched cultures. Mol Cell Neurosci. 1991; 2(3):235-243.
• Childs GV, Rougeau D, Unabia G. Corticotropin-releasing hormone and epidermal growth factor: mitogens for anterior pituitary corticotropes. Endocrinology. 1995; 136(4):1595-1602.
• Childs GV, Unabia G. Epidermal growth factor and gonadotropin-releasing hormone stimulate proliferation of enriched population of gonadotropes. Endocrinology. 2001; 142(2):847-853.
• Cohen S. Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal. J Biol Chem. 1962; 237:1555-1562.
• Coimbra TM, Cieslinski DA, Humes HD. Epidermal growth factor accelerates renal repair in mercuric chloride nephrotoxicity. Am J Physiol. 1990; 259(3 Pt 2):F438-443.
• Collier RJ, McGrath MF, Byatt JC, Zurfluh LL. Regulation of bovine mammary gland growth by peptide hormones: involvement of receptors, growth factors and binding proteins. Livest Prod Sci. 1993; 35:21-33.
• Corps AN, Brigstock DR, Littlewood CJ, Brown KD. Receptors for epidermal growth factor and insulin-like growth factor-I on preimplantation trophoderm of the pig. Development. 1990; 110(1):221-227.
• Cribbs RK, Luquette MH, Besner GE. Acceleration of partial-thickness burn wound healing with topical application of heparin-binding EGF-like growth factor (HB-EGF). J Burn Care Rehabil. 1998; 2:95-101.
• Dadi TD, Li MW, Lloyd KC. EGF and TGF-alpha supplementation enhances development of cloned mouse embryos. Cloning Stem Cells. 2007; 9(3):315-326.
• Danto SI, Borok Z, Zhang XL, Lopez MZ, Patel P, Crandall ED, Lubman RL. Mechanisms of EGF-induced stimulation of sodium reabsorption by alveolar epithelial cells. Am J Physiol. 1998; 275(1):82-92.
• 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. Epidermal growth factor enhances osteogenic differentiation of dental pulp stem cells in vitro. Head Face Med. 2015; 11:29.
• Dvorak B. Milk epidermal growth factor and gut protection. J Pediatr. 2010; 156:31-35.
• Duh G, Mouri N, Warburton D, Thomas DW. EGF regulates early embryonic mouse gut development in chemically defined organ culture. Pediatr Res. 2000; 48(6):794-802.
• Earp HS, Dawson TL, Li X, Yu H. Heterodimerization and functional interaction between EGF receptor family members: a new signaling paradigm with implications for breast cancer research. Breast Cancer Res Treat. 1995; 35(1):115-132.
• Ertugrul BM, Buke C, Ersoy OS, Ay B, Demirez DS, Savk O. Intralesional epidermal growth factor for diabetic foot wounds: the first cases in Turkey. Diabet Foot Ankle. 2015; 6:28419.
• Fallon JH, Seroogy KB, Loughlin SE, Morrison RS, Bradshaw RA, Knaver DJ, Cunningham DD. Epidermal growth factor immunoreactive material in the central nervous system: location and development. Science. 1984; 224(4653):1107-1109.
• Fernández-Montequín JI, Valenzuela-Silva CM, Díaz OG, Savigne W, Sancho-Soutelo N, Rivero-Fernández F, Sánchez-Penton P, Morejón-Vega L, Artaza-Sanz H, García-Herrera A, González-Benavides C, Hernández-Cañete CM, Vázquez-Proenza A, Berlanga-Acosta J, López-Saura PA; Cuban Diabetic Foot Study Group. Intra-lesional injections of recombinant human epidermal growth factor promote granulation and healing in advanced diabetic foot ulcers: multicenter,randomised, placebo-controlled, double-blind study. Int Wound J. 2009; 6:432-443.
• Ferrari G, Toffano G, Skaper SD. Epidermal growth factor exerts neuronotrophic effects on dopaminergic and GABAergic CNS neurons: comparison with basic fibroblast growth factor. J Neurosci Res. 1991; 30:493-497.
• Fischer B, Rose-Hellekant TA, Sheffield LG, Bertics PJ, Bavister BD. Binding of epidermal growth factor and transforming growth factor-a in mammalian preimplantation embryos. Theriogenology. 1994; 41:879-887.
• Foltzer-Jourdainne C, Garaud JC, Nsi-Emvo E, Raul F. Epidermal growth factor and the maturation of intestinal sucrase in suckling rats . Am J Physiol. 1993; 265:459-466.
• Futamura T, Toyooka K, Iritani S, Niizato K, Nakamura R, Tsuchiya K, Someya T, Kakita A, Takahashi H, Nawa H. Abnormal expression of epidermal growth factor and its receptor in the forebrain and serum of schizophrenic patients. Mol Psychiatry. 2002; 7(7):673-682.
• Gharib-Hamrouche N, Chêne N, Guillomot M, Martal J. Localization and characterization of EGF/TGF-alpha receptors on peri-implantation trophoblast in sheep. J Reprod Fertil. 1993; 98(2):385-392.
• Gómez-Pinilla F, Knauer DJ, Nieto-Sampedro M. Epidermal growth factor receptor immunoreactivity in rat brain. Development and cellular localization. Brain Res. 1988; 438(1-2):385-390.
• Good M, Sodhi CP, Egan CE, Afrazi A, Jia H, Yamaguchi Y, Lu P, Branca MF, Ma C, Prindle T Jr, Mielo S, Pompa A, Hodzic Z, Ozolek JA, Hackam DJ. Breast milk protects against the development of necrotizing enterocolitis through inhibition of Toll-like receptor 4 in the intestinal epithelium via activation of the epidermal growth factor receptor. Mucosal Immunol. 2015; 5:1166-1179.
• Gospodarowicz D, Greenburg G. The effects of epidermal and fibroblast growth factors on the repair of corneal endothelial wounds in bovine corneas maintained in organ culture. Exp Eye Res, 1979; 28(2):147-157.
• Göritz F, Jewgenow K, Meyer HH. Epidermal growth factor and epidermal growth factor receptor in the ovary of the domestic cat (Felis catus). J Reprod Fertil. 1996; 106(1):117-124.
• Grazul-Bilska AT, Choi JT, Bilski JJ, Weigl RM, Kirsch JD, Kraft KC, Reynolds LP, Redmer DA. Effects of epidermal growth factor on early embryonic development after in vitro fertilization of oocytes collected from ewes treated with follicle stimulating hormone. Theriogenology. 2003; 59(5-6):1449-1457.
• Gritti A, Frölichsthal-Schoeller P, Galli R, Parati EA, Cova L, Pagano SF, Bjornson CR, Vescovi AL. Epidermal and fibroblast growth factors behave as mitogenic regulators for a single multipotent stem cell-like population from the subventricular region of the adult mouse forebrain. J Neurosci. 1999; 19(9):3287-3297.
• Hofmann GE, Anderson TL. Immunohistochemical localization of epidermal growth factor receptor during implantation in the rabbit. Am J Obstet Gynecol. 1990; 162(3):837-841.
• Hong JP, Jung HD, Kim YW. Recombinant human epidermal growth factor (EGF) to enhance healing for diabetic foot ulcers. Ann Plast Surg. 2006;56(4):394-398.
• Humes HD, Cieslinski DA, Coimbra TM, Messana JM, Glavao C. Epidermal growth factor enhances renal tubule cell regeneration and repair and accelerates the recovery of renal failure. J Clin Invest 1989; 84:1757-1761.
• Hussein Ael-A, Shokeir AA, Sarhan ME, El-Menabawy FR, Abd-Elmoneim HA, El-Nashar EM, Barakat NM. Effects of combined erythropoietin and epidermal growth factor on renal ischaemia/reperfusion injury: a randomized experimental controlled study. BJU Int. 2011; 107(2):323-328.
• Ikeda H, Mitsuhashi T, Kubota K, Kuzuya N, Uchimura H. Epidermal growth factor stimulates growth hormone secretion from superfused rat adenohypophyseal fragments. Endocrinology. 1984; 115(2):556-558.
• Ishiyama J, Saito H, Abe K. Epidermal growth factor and basic fibroblast growth factor promote the generation of long-term potentiation in the dentate gyrus of anaesthetized rats. Neurosci Res. 1991; 12(3):403-411.
• Jansson T, Skarland H. Maternally administered epidermal growth factor stimulates fetal growth in the rat. Acta Physiol Scand 1990; 138:245-246.
• Jeffrey SC, Murray MJ, Eichorn ES. Distribution of epidermal growth factor receptor (EGFr) in normal and acute peptic-injured equine gastric squamous epithelium. Equine Vet J. 2001; 33(6):562-569.
• Jeong W, Jung S, Bazer FW, Song G, Kim J. Epidermal growth factor: Porcine uterine luminal epithelial cell migratory signal during the peri-implantation period of pregnancy. Mol Cell Endocrinol. 2016; 420:66-74.
• Jeong W, Kim J, Bazer FW, Song G. Epidermal growth factor stimulates proliferation and migration of porcine trophectoderm cells through protooncogenic protein kinase 1 and extracellular-signal-regulated kinases 1/2 mitogen-activated protein kinase signal transduction cascades during early pregnancy. Mol Cell Endocrinol. 2013; 381(1-2):302-11.
• Johnson LK, Baxter JD, Vlodavsky I, Gospodarowicz D. Epidermal growth factor and expression of specific genes: effects on cultured rat pituitary cells are dissociable from the mitogenic response. Proc Natl Acad Sci U S A. 1980; 77(1):394-398.
• Johnstone ED, Mackova M, Das S, Payne SG, Lowen B, Sibley CP, Chan G, Guilbert LJ. Multiple anti-apoptotic pathways stimulated by EGF in cytotrophoblasts. Placenta. 2005; 26(7):548-555.
• Jorissen RN, Walker F, Pouliot N, Garrett TP, Ward CW, Burgess AW. Epidermal growth factor receptor: mechanisms of activation and signalling. Exp Cell Res. 2003; 284(1):31-53.
• Jost M, Kari C, Rodeck U. The EGF receptor - an essential regulator of multiple epidermal functions. Eur J Dermatol. 2000; 10(7):505-510.
• Kajikawa K, Yasui W, Sumiyoshi H, Yoshida K, Nakayama H, Ayhan A, Yokozaki H, Ito H, Tahara E. Expression of epidermal growth factor in human tissues. Immunohistochemical and biochemical analysis. Virchows Arch A Pathol Anat Histopathol. 1991; 418(1):27-32.
• Kelly EJ, Newell SJ, Brownlee KG, Farmery SM, Cullinane C, Reid WA, Jackson P, Gray SF, Primrose JN, Lagopoulos M. Role of epidermal growth factor and transforming growth factor alpha in the developing stomach. Arch Dis Child Fetal Neonatal Ed. 1997; 76(3):158-162.
• Kennedy WA 2nd, Buttyan R, Garcia-Montes E, D'Agati V, Olsson CA, Sawczuk IS. Epidermal growth factor suppresses renal tubular apoptosis following ureteral obstruction. Urology. 1997; 49(6):973-980.
• Khurana S, Nath SK, Levine SA, Bowser JM, Tse CM, Cohen ME, Donowitz M. Brush border phosphatidylinositol 3-kinase mediates epidermal growth factor stimulation of intestinal NaCl absorption and Na+/H+ exchange. J Biol Chem. 1996; 271(17):9919-9927.
• Kim D, Kim SY, Mun SK, Rhee S, Kim BJ. Epidermal growth factor improves the migration and contractility of aged fibroblasts cultured on 3D collagen matrices. Int J Mol Med. 2015; 35(4):1017-1025.
• Kim YJ, Lee GS, Hyun SH, Ka HH, Choi KC, Lee CK, Jeung EB. Uterine expression of epidermal growth factor family during the course of pregnancy in pigs. Reprod Domest Anim. 2009; 44(5):797-804.
• Kingsnorth AN, Vowles R, Nash JR. Epidermal growth factor increases tensile strength in intestinal wounds in pigs. Br J Surg. 1990; 77(4):409-412.
• Konturek SJ, Dembinski A, Warzecha Z, Brzozowski T, Gregory H. Role of epidermal growth factor in healing of chronic gastroduodenal ulcers in rats. Gastroenterology. 1988; 94(6):1300-1307.
• Konturek JW, Brzozowski T, Konturek SJ. Epidermal growth factor in protection, repair, and healing of gastroduodenal mucosa. J Clin Gastroenterol. 1991; 13 Suppl 1:S88-97.
• Kornblum HI, Hussain R, Wiesen J, Miettinen P, Zurcher SD, Chow K, Derynck R, Werb Z. Abnormal astrocyte development and neuronal death in mice lacking the epidermal growth factor receptor. J Neurosci Res. 1998; 53(6):697-717.
• Kushikata T, Fang J, Chen Z, Wang Y, Krueger JM. Epidermal growth factor enhances spontaneous sleep in rabbits. Am J Physiol. 1998; 275(2 Pt 2):R509-514.
• Lazar LM, Blum M. Regional distribution and developmental expression of epidermal growth factor and transforming growth factor-alpha mRNA in mouse brain by a quantitative nuclease protection assay. Brain Res Dev Brain Res. 1991 ;60(2):145-154.
• Lee H, Hansson HA, Norström E, Helander HF. Immunoreactivities for epidermal growth factor (EGF) and for EGF receptors in rats with gastric ulcers. Cell Tissue Res. 1991; 265(2):211-218.
• Lemmon MA, Schlessinger J. Regulation of signal transduction and signal diversity by receptor oligomerization. Trends Biochem Sci. 1994; 19(11):459-463.
• Lennard SN, Gerstenberg C, Allen WR, Stewart F. Expression of epidermal growth factor and its receptor in equine placental tissues. J Reprod Fertil. 1998; 112(1):49-57.
• Lonergan P, Carolan C, Van Langendonckt A, Donnay I, Khatir H, Mermillod P. Role of epidermal growth factor in bovine oocyte maturation and preimplantation embryo development in vitro. Biol Reprod. 1996; 54(6):1420-1429.
• Luck MS, Bass P. Effect of epidermal growth factor on experimental colitis in the rat. J Pharmacol Exp Ther. 1993; 264(2):984-990.
• Malcherek P, Schultz G, Wingren U, Franzén L. Formation of healing tissue and angiogenesis in repair of connective tissue stimulated by epidermal growth factor. Scand J Plast Reconstr Surg Hand Surg. 1994; 28(1):1-7.
• Marti U, Burwen SJ, Jones AL. Biological effects of epidermal growth factor, with emphasis on the gastrointestinal tract and liver: an update. Hepatology. 1989; 9(1):126-138.
• Maruo T, Ladines-Llave CA, Samoto T, Matsuo H, Manalo AS, Ito H, Mochizuki M. Expression of epidermal growth factor and its receptor in the human ovary during follicular growth and regression. Endocrinology. 1993; 132(2):924-931.
• Massagué J, Pandiella A. Membrane-anchored growth factors. Annu Rev Biochem. 1993; 62:515-541.
• Miettinen PJ, Berger JE, Meneses J, Phung Y, Pedersen RA, Werb Z, Derynck R. Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor. Nature. 1995; 376(6538):337-341.
• Morin NJ, Laurent G, Nonclercq D, Toubeau G, Heuson-Stiennon JA, Bergeron MG, Beauchamp D. Epidermal growth factor accelerates renal tissue repair in a model of gentamicin nephrotoxicity in rats. Am J Physiol. 1992; 263(5 Pt 2):F806-811.
• Morrison RS, Kornblum HI, Leslie FM, Bradshaw RA. Trophic stimulation of cultured neurons from neonatal rat brain by epidermal growth factor. Science. 1987; 238(4823):72-75.
• Murdoch GH, Potter E, Nicolaisen AK, Evans RM, Rosenfeld MG. Epidermal growth factor rapidly stimulates prolactin gene transcription. Nature. 1982; 300(5888):192-194.
• Nielsen LL, Werb Z, Pedersen RA. Induction of c-fos transcripts in early postimplantation mouse embryos by TGF-alpha, EGF, PDGF, and FGF. Mol Reprod Dev. 1991; 29(3):227-237.
• Nieto-Sampedro M, Gómez-Pinilla F, Knauer DJ, Broderick JT. Epidermal growth factor receptor immunoreactivity in rat brain astrocytes. Response to injury. Neurosci Lett. 1988; 91(3):276-282.
• Ninomiya M, Yamashita T, Araki N, Okano H, Sawamoto K. Enhanced neurogenesis in the ischemic striatum following EGF-induced expansion of transit-amplifying cells in the subventricular zone. Neurosci Lett. 2006; 403(1-2):63-67.
• Norman J, Tsau YK, Bacay A, Fine LG. Epidermal growth factor accelerates functional recovery from ischaemic acute tubular necrosis in the rat: role of the epidermal growth factor receptor. Clin Sci (Lond). 1990; 78(5):445-450.
• Ogiso H, Ishitani R, Nureki O, Fukai S, Yamanaka M, Kim JH, Saito K, Sakamoto A, Inoue M, Shirouzu M, Yokoyama S. Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains. Cell. 2002; 110(6):775-787.
• Okita K, Karita M, Nakanishi N, Takemoto T. Role of epidermal growth factor in protection and repair of gastric mucosal injury. J Clin Gastroenterol. 1991; 13 Suppl 1:S103-108.
• Okuyama H, Urao M, Lee D, Drongowski RA, Coran AG. The effect of epidermal growth factor on bacterial translocation in newborn rabbits. J Pediatr Surg. 1998; 33:225-228.
• Oomizu S, Honda J, Takeuchi S, Kakeya T, Masui T, Takahashi S. Transforming growth factor-alpha stimulates proliferation of mammotrophs and corticotrophs in the mouse pituitary. J Endocrinol. 2000; 165(2):493-501.
• Pan Y, Cui Y, Yu S, Zhang Q, Fan J, Abdul Rasheed B, Yang K. The expression of epidermal growth factor (EGF) and its receptor (EGFR) during post-natal testes development in the yak. Reprod Domest Anim. 2014; 49(6):970-976.
• Park GH, Rhee do Y, Moon HR, Won CH, Lee MW, Choi JH, Moon KC, Chang SE. Effect of an epidermal growth factor-containing cream on postinflammatory hyperpigmentation after Q-switched 532-nm neodymium-doped yttrium aluminum garnet laser treatment. Dermatol Surg. 2015; 41(1):131-135.
• Playford RJ, Hanby AM, Gschmeissner S, Peiffer LP, Wright NA, McGarrity T. The epidermal growth factor receptor (EGF-R) is present on the basolateral, but not the apical, surface of enterocytes in the human gastrointestinal tract. Gut 1996; 39(2):262-266.
• Pollack PF, Goda T, Colony PC, Edmond J, Thornburg W, Korc M, Koldovský O. Effects of enterally fed epidermal growth factor on the small and large intestine of the suckling rat. Regul Pept. 1987; 17:121-132.
• Prigent SA, Lemoine NR. The type 1 (EGFR-related) family of growth factor receptors and their ligands. Prog Growth Factor Res. 1992; 4(1):1-24.
• Procaccino F, Reinshagen M, Hoffmann P, Zeeh JM, Lakshmanan J, McRoberts JA, Patel A, French S, Eysselein VE. Protective effect of epidermal growth factor in an experimental model of colitis in rats. Gastroenterology. 1994; 107(1):12-17.
• Raphael B, Kerr NC, Shimizu RW, Lass JH, Crouthamel KC, Glaser SR, Stern GA, McLaughlin BJ, Musch DC, Duzman E. Enhanced healing of cat corneal endothelial wounds by epidermal growth factor. Invest Ophthalmol Vis Sci. 1993; 34(7):2305-2312.
• Rich LF, Hatfield JM, Louiselle I. The influence of epidermal growth factor on cat corneal endothelial wound healing. Curr Eye Res. 1991; 10(9):823-830.
• Rodriguez Salgueiro S, González Núñez L, García Del Barco Herrera D, Santos Febles E, Maza Ares D, Millares López R, Berlanga Acosta J. Role of epidermal growth factor and growth hormone-releasing peptide-6 in acceleration of renal tissue repair after kanamycin overdosing in rats. Iran J Kidney Dis. 2014; 8(5):382-388.
• Safari M, Ghahari L, Zoroufchi MD. Effects of epidermal growth factor, platelet derived growth factor and growth hormone on cultured rat keratinocytes cells in vitro. Pak J Biol Sci. 2014; 7:931-936.
• Savage CR Jr, Hash JH, Cohen S. Epidermal growth factor. Location of disulfide bonds. J Biol Chem. 1973; 248(22):7669-7672.
• Scafidi J, Hammond TR, Scafidi S, Ritter J, Jablonska B, Roncal M, Szigeti-Buck K, Coman D, Huang Y, McCarter RJ Jr, Hyder F, Horvath TL, Gallo V. Intranasal epidermal growth factor treatment rescues neonatal brain injury. Nature. 2014; 506(7487):230-234.
• Schaudies RP, Christian EL, Savage CR Jr. Epidermal growth factor immunoreactive material in the rat brain. Localization and identification of multiple species. J Biol Chem. 1989; 264(18):10447-10450.
• Schneider MR, Wolf E. The epidermal growth factor receptor ligands at a glance. J Cell Physiol. 2009; 218(3):460-466.
• Schonbrunn A, Krasnoff M, Westendorf JM, Tashjian AH Jr. Epidermal growth factor and thyrotropin-releasing hormone act similarly on a clonal pituitary cell strain. Modulation of hormone production and inhbition of cell proliferation. J Cell Biol. 1980; 85(3):786-97.
• Sheffield LG. Mastitis increases growth factor messenger ribonucleic acid in bovine mammary glands. J Dairy Sci. 1997; 80 (9):2020-2024.
• Sibilia M, Wagner EF. Strain-dependent epithelial defects in mice lacking the EGF receptor. Science. 1995; 269(5221):234-238.
• Sibilia M, Steinbach JP, Stingl L, Aguzzi A, Wagner EF. A strain-independent postnatal neurodegeneration in mice lacking the EGF receptor. EMBO J. 1998; 17(3):719-731.
• Sibilia M, Wagner B, Hoebertz A, Elliott C, Marino S, Jochum W, Wagner EF. Mice humanised for the EGF receptor display hypomorphic phenotypes in skin, bone and heart. Development. 2003; 130(19):4515-4525.
• Singh B, Rutledge JM, Armstrong DT. Epidermal growth factor and its receptor gene expression and peptide localization in porcine ovarian follicles. Mol Reprod Dev. 1995; 40(4):391-399.
• Smith K, LeJeune S, Harris AH, Rees MC. Epidermal growth factor receptor in human uterine tissues. Hum Reprod. 1991; 6(5):619-622.
• Stewart F, Power CA, Lennard SN, Allen WR, Amet L, Edwards RM. Identification of the horse epidermal growth factor (EGF) coding sequence and its use in monitoring EGF gene expression in the endometrium of the pregnant mare. J Mol Endocrinol. 1994; 12(3):341-350.
• Su Z, Ma H, Wu Z, Zeng H, Li Z, Wang Y, Liu G, Xu B, Lin Y, Zhang P, Wei X. Enhancement of skin wound healing with decellularized scaffolds loaded with hyaluronic acid and epidermal growth factor. Mater Sci Eng C Mater Biol Appl. 2014; 44:440-448.
• Sun D, Bullock MR, Altememi N, Zhou Z, Hagood S, Rolfe A, McGinn MJ, Hamm R, Colello RJ. The effect of epidermal growth factor in the injured brain after trauma in rats. J Neurotrauma. 2010; 27(5):923-938.
• Tarnawski A, Stachura J, Durbin T, Sarfeh IJ, Gergely H. Increased expression of epidermal growth factor receptor during gastric ulcer healing in rats. Gastroenterology. 1992; 102(2):695-698.
• Tarnawski AS, Jones MK. The role of epidermal growth factor (EGF) and its receptor in mucosal protection, adaptation to injury, and ulcer healing: involvement of EGF-R signal transduction pathways. J Clin Gastroenterol. 1998; 27 Suppl 1:S12-20.
• Teramoto T, Qiu J, Plumier JC, Moskowitz MA. EGF amplifies the replacement of parvalbumin-expressing striatal interneurons after ischemia. J Clin Invest. 2003; 111(8):1125-1132.
• Thompson JF. Specific receptors for epidermal growth factor in rat intestinal microvillus membranes. Am J Physiol. 1988; 254(3):429-435.
• Tsang MW, Wong WK, Hung CS, Lai KM, Tang W, Cheung EY, Kam G, Leung L, Chan CW, Chu CM, Lam EK. Human epidermal growth factor enhances healing of diabetic foot ulcers. Diabetes Care. 2003; 26(6):1856-1861.
• Tuyet HL, Nguyen Quynh TT, Vo Hoang Minh H, Thi Bich DN, Do Dinh T, Le Tan D, Van HL, Le Huy T, Doan Huu H, Tran Trong TN. The efficacy and safety of epidermal growth factor in treatment of diabetic foot ulcers: the preliminary results. Int Wound J. 2009; 6(2):159-166.
• Usuki Y, Katakami C, Yamamoto M. The effect of Epidermal Growth Factor on Keratocytes During Healing of Corneal Penelrating Incision. Nippon Ganka Gakkai Zasshi. 1995; 99(11):1209-1213.
• Vehaskari VM, Herndon J, Hamm LL. Mechanism of sodium transport inhibition by epidermal growth factor in cortical collecting ducts. Am J Physiol. 1991; 261(5):896-903.
• Wandji SA, Pelletier G, Sirard MA. Ontogeny and cellular localization of 2 'I-labeled basic fibroblast growth factor and '2 51-labeled epidermal growth factor binding sites in ovaries from bovine fetuses and neonatal calves. Biol Reprod. 1992; 47:807-813.
• Wang Y, Pennock S, Chen X, Wang Z. Endosomal signaling of epidermal growth factor receptor stimulates signal transduction pathways leading to cell survival. Mol Cell Biol. 2002; 22(20):7279-7290.
• Warner BW, Warner BB. Role of epidermal growth factor in the pathogenesis of neonatal necrotizing enterocolitis. Semin Pediatr Surg. 2005; 3:175-180.
• Wei Z, Park KW, Day BN, Prather RS. Effect of epidermal growth factor on preimplantation development and its receptor expression in porcine embryos. Mol Reprod Dev. 2001; 60(4):457-462.
• Weiss FU, Daub H, Ullrich A. Novel mechanisms of RTK signal generation. Curr Opin Genet Dev. 1997; 7(1):80-86.
• Wiedermann CJ, Jelesof NJ, Pert CB, Hill JM, Braunsteiner H. Neuromodulation by polypeptide growth factors: preliminary results on the distribution of epidermal growth factor receptors in adult brain. Wien Klin Wochenschr. 1988; 100(23):760-763.
• Wilson SE, He YG, Weng J, Zieske JD, Jester JV, Schultz GS. Effect of epidermal growth factor, hepatocyte growth factor, and keratinocyte growth factor, on proliferation, motility and differentiation of human corneal epithelial cells. Exp Eye Res, 1994; 59(6):665-678.
• Wu Z, Tang Y, Fang H, Su Z, Xu B, Lin Y, Zhang P, Wei X. Decellularized scaffolds containing hyaluronic acid and EGF for promoting the recovery of skin wounds. J Mater Sci Mater Med. 2015; 1:5322.
• Yamada M, Ikeuchi T, Hatanaka H. The neurotrophic action and signalling of epidermal growth factor. Prog Neurobiol. 1997; 51(1):19-37.
• Yera-Alos IB, Alonso-Carbonell L, Valenzuela-Silva CM, Tuero-Iglesias AD, Moreira-Martínez M, Marrero-Rodríguez I, López-Mola E, López-Saura PA. Active post-marketing surveillance of the intralesional administration of human recombinant epidermal growth factor in diabetic foot ulcers. BMC Pharmacol Toxicol. 2013; 3:14-44.
• Zeineldin R, Hudson LG. Epithelial cell migration in response to epidermal growth factor. Methods Mol Biol. 2006; 327:147-158.
• Zheng B, Ye L, Zhou Y, Zhu S, Wang Q, Shi H, Chen D, Wei X, Wang Z, Li X, Xiao J, Xu H, Zhang H. Epidermal growth factor attenuates blood-spinal cord barrier disruption via PI3K/Akt/Rac1 pathway after acute spinal cord injury. J Cell Mol Med. 2016 Jan 15. doi: 10.1111/jcmm.12761.
• Zijlstra RT, Odle J, Hall WF, Petschow BW, Gelberg HB, Litov RE. Effect of orally administered epidermal growth factor on intestinal recovery of neonatal pigs infected with rotavirus. J Pediatr Gastroenterol Nutr. 1994; 19(4):382-90