Ukr.Biochem.J. 2024; Том 96, № 5, вересень-жовтень, c. 5-20

doi: https://doi.org/10.15407/ubj96.05.005

Гепарин-зв’язувальний EGF-подібний фактор росту: механізми біологічної активності та потенційні терапевтичні застосування

04.04.2025   Uncategorized   No comments

Л. М. Дронько1, Т. М. Луценко1*, Н. В. Короткевич2,
І. О. Вовк2, Д. А. Жукова2, С. І. Романюк2,
А. А. Сіромолот2, А. Ю. Лабинцев2, Д. В. Колибо2

1Національний технічний університет України
«Київський політехнічний інститут імені Ігоря Сікорського», Київ, Україна;
2Інститут біохімії ім. О.В. Палладіна НАН України, Київ, Україна;
*e-mail: lutsenko.tetiana@lll.kpi.ua

Отримано: 06 серпня 2024; Виправлено: 18 вересня 2024;
Затверджено: 07 жовтня 2024; Доступно онлайн: 28 жовтня 2024

Рецептор дифтерійного токсину на чутливих клітинах ссавців відомий як закріплений на мембрані попередник гепарин-зв’язувального EGF-подібного фактора росту (HB-EGF). Коли попередник розщеплюється металопротеїназами, утворюється розчинна форма (sHB-EGF), яка може зв’язуватися з рецепторами EGF, що призводить до активації сигнальних шляхів, які регулюють клітинну проліферацію, диференціювання, міграцію та інгібування апоптозу. Здатність HB-EGF спричинювати як позитивні, так і негативні наслідки для організму підкреслює складність його біологічних функцій і потреби в тонкому розумінні його ролі в здоровому організмі та за різних захворювань. В огляді узагальнено дані про структуру HB-EGF, біологічну активність, участь у механізмі дії дифтерійного токсину, загоєння ран, пухлинну прогресію, а також способи доставки HB-EGF.

Ключові слова: , , , , ,

Посилання:

  1. Dao DT, Anez-Bustillos L, Adam RM, Puder M, Bielenberg DR. Heparin-Binding Epidermal Growth Factor-Like Growth Factor as a Critical Mediator of Tissue Repair and Regeneration. Am J Pathol. 2018;188(11):2446-2456. PubMed, PubMedCentral, CrossRef
  2. Dreux AC, Lamb DJ, Modjtahedi H, Ferns GA. The epidermal growth factor receptors and their family of ligands: their putative role in atherogenesis. Atherosclerosis. 2006;186(1):38-53. PubMed, CrossRef
  3. Higashiyama S, Abraham JA, Miller J, Fiddes JC, Klagsbrun M. A heparin-binding growth factor secreted by macrophage-like cells that is related to EGF. Science. 1991;251(4996):936-939. PubMed, CrossRef
  4. Murphrey MB, Quaim L, Rahimi N, Varacallo M. Biochemistry, epidermal growth factor receptor. In: StatPearls. Treasure Island (FL): StatPearls Publishing. 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482459/ PubMed
  5. Chudina TO, Labintsev AJ, Romaniuk SI, Kolybo DV, Komisarenko SV. Changes in proHB-EGF expression after functional activation of the immune system cells. Ukr Biochem J. 2017;89(6):31-38. CrossRef
  6. Higashiyama S, Lau K, Besner GE, Abraham JA, Klagsbrun M. Structure of heparin-binding EGF-like growth factor. Multiple forms, primary structure, and glycosylation of the mature protein. J Biol Chem. 1992;267(9):6205-6212. PubMed, CrossRef
  7. Vinante F, Rigo A. Heparin-binding epidermal growth factor-like growth factor/diphtheria toxin receptor in normal and neoplastic hematopoiesis. Toxins (Basel). 2013;5(6):1180-1201. PubMed, PubMedCentral, CrossRef
  8. Massagué J, Pandiella A. Membrane-anchored growth factors. Annu Rev Biochem. 1993:62:515-541.
    PubMed, CrossRef
  9. Raab G, Higashiyama S, Hetelekidis S, Abraham JA, Damm D, Ono M, Klagsbrun M. Biosynthesis and processing by phorbol ester of the cells surface-associated precursor form of heparin-binding EGF-like growth factor. Biochem Biophys Res Commun. 1994;204(2):592-597. PubMed, CrossRef
  10. Izumi Y, Hirata M, Hasuwa H, Iwamoto R, Umata T, Miyado K, Tamai Y, Kurisaki T, Sehara-Fujisawa A, Ohno S, Mekada E. A metalloprotease-disintegrin, MDC9/meltrin-gamma/ADAM9 and PKCdelta are involved in TPA-induced ectodomain shedding of membrane-anchored heparin-binding EGF-like growth factor. EMBO J. 1998;17(24):7260-7272. PubMed, PubMedCentral, CrossRef
  11. Weskamp G, Cai H, Brodie TA, Higashyama S, Manova K, Ludwig T, Blobel CP. Mice lacking the metalloprotease-disintegrin MDC9 (ADAM9) have no evident major abnormalities during development or adult life. Mol Cell Biol. 2002;22(5):1537-1544. PubMed, PubMedCentral, CrossRef
  12. Asakura M, Kitakaze M, Takashima S, Liao Y, Ishikura F, Yoshinaka T, Ohmoto H, Node K, Yoshino K, Ishiguro H, Asanuma H, Sanada S, Matsumura Y, Takeda H, Beppu S, Tada M, Hori M, Higashiyama S. Cardiac hypertrophy is inhibited by antagonism of ADAM12 processing of HB-EGF: metalloproteinase inhibitors as a new therapy. Nat Med. 2002;8(1):35-40. PubMed, CrossRef
  13. Yan Y, Shirakabe K, Werb Z. The metalloprotease Kuzbanian (ADAM10) mediates the transactivation of EGF receptor by G protein-coupled receptors. J Cell Biol. 2002;158(2):221-226. PubMed, PubMedCentral, CrossRef
  14. Dethlefsen SM, Raab G, Moses MA, Adam RM, Klagsbrun M, Freeman MR. Extracellular calcium influx stimulates metalloproteinase cleavage and secretion of heparin-binding EGF-like growth factor independently of protein kinase C. J Cell Biochem. 1998;69(2):143-153. PubMed, CrossRef
  15. Goishi K, Higashiyama S, Klagsbrun M, Nakano N, Umata T, Ishikawa M, Mekada E, Taniguchi N. Phorbol ester induces the rapid processing of cell surface heparin-binding EGF-like growth factor: conversion from juxtacrine to paracrine growth factor activity. Mol Biol Cell. 1995;6(8):967-980. PubMed, PubMedCentral, CrossRef
  16. Takenobu H, Yamazaki A, Hirata M, Umata T, Mekada E. The stress- and inflammatory cytokine-induced ectodomain shedding of heparin-binding epidermal growth factor-like growth factor is mediated by p38 MAPK, distinct from the 12-O-tetradecanoylphorbol-13-acetate- and lysophosphatidic acid-induced signaling cascades. J Biol Chem. 2003;278(19):17255-17262. PubMed, CrossRef
  17. Roudabush FL, Pierce KL, Maudsley S, Khan KD, Luttrell LM. Transactivation of the EGF receptor mediates IGF-1-stimulated shc phosphorylation and ERK1/2 activation in COS-7 cells. J Biol Chem. 2000;275(29):22583-22589. PubMed, CrossRef
  18. Nanba D, Inoue H, Shigemi Y, Shirakata Y, Hashimoto K, Higashiyama S. An intermediary role of proHB-EGF shedding in growth factor-induced c-Myc gene expression. J Cell Physiol. 2008;214(2):465-473. PubMed, CrossRef
  19. Tanida S, Joh T, Itoh K, Kataoka H, Sasaki M, Ohara H, Nakazawa T, Nomura T, Kinugasa Y, Ohmoto H, Ishiguro H, Yoshino K, Higashiyama S, Itoh M. The mechanism of cleavage of EGFR ligands induced by inflammatory cytokines in gastric cancer cells. Gastroenterology. 2004;127(2):559-569.
    PubMed, CrossRef
  20. Filardo EJ, Quinn JA, Bland KI, Frackelton AR Jr. Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF. Mol Endocrinol. 2000;14(10):1649-1660. PubMed, CrossRef
  21.  Uchiyama-Tanaka Y, Matsubara H, Nozawa Y, Murasawa S, Mori Y, Kosaki A, Maruyama K, Masaki H, Shibasaki Y, Fujiyama S, Nose A, Iba O, Hasagawa T, Tateishi E, Higashiyama S, Iwasaka T. Angiotensin II signaling and HB-EGF shedding via metalloproteinase in glomerular mesangial cells. Kidney Int. 2001;60(6):2153-2163. PubMed, CrossRef
  22. Higashiyama S, Iwabuki H, Morimoto C, Hieda M, Inoue H, Matsushita N. Membrane-anchored growth factors, the epidermal growth factor family: beyond receptor ligands. Cancer Sci. 2008;99(2):214-220. PubMed, PubMedCentral, CrossRef
  23. Naglich JG, Metherall JE, Russell DW, Eidels L. Expression cloning of a diphtheria toxin receptor: identity with a heparin-binding EGF-like growth factor precursor. Cell. 1992;69(6):1051-1061. PubMed, CrossRef
  24. Van Ness BG, Howard JB, Bodley JW. ADP-ribosylation of elongation factor 2 by diphtheria toxin. Isolation and properties of the novel ribosyl-amino acid and its hydrolysis products. J Biol Chem. 1980;255(22):10717-10720. PubMed, CrossRef
  25. Lord JM, Smith DC, Roberts LM. Toxin entry: how bacterial proteins get into mammalian cells. Cell Microbiol. 1999;1(2):85-91. PubMed, CrossRef
  26. Louie GV, Yang W, Bowman ME, Choe S. Crystal structure of the complex of diphtheria toxin with an extracellular fragment of its receptor. Mol Cell. 1997;1(1):67-78. PubMed, CrossRef
  27. Kolibo DV, Romanyuk SI, Radavskiy YuL, Komisarenko SV. Effect of diphtheria toxin on the viability of phagocytes and B-lymphocytes in animals sensitive and insensitive to it. Ukr Biokhim Zhurn. 2002;74(2):30-36. (In Russian). PubMed
  28. Higashiyama S, Nanba D. ADAM-mediated ectodomain shedding of HB-EGF in receptor cross-talk. Biochim Biophys Acta. 2005;1751(1):110-117. PubMed, CrossRef
  29. Nishi E, Prat A, Hospital V, Elenius K, Klagsbrun M. N-arginine dibasic convertase is a specific receptor for heparin-binding EGF-like growth factor that mediates cell migration. EMBO J. 2001;20(13):3342-3350. PubMed, PubMedCentral, CrossRef
  30. Nishi E, Hiraoka Y, Yoshida K, Okawa K, Kita T. Nardilysin enhances ectodomain shedding of heparin-binding epidermal growth factor-like growth factor through activation of tumor necrosis factor-alpha-converting enzyme. J Biol Chem. 2006;281(41):31164-31172. PubMed, CrossRef
  31. Krynina OI, Korotkevych NV, Labyntsev AJ, Romaniuk SI, Kolybo DV, Komisarenko SV. Influence of human HB-EGF secreted form on cells with different EGFR and ErbB4 quantity. Ukr Biochem J. 2019;91(5):25-33. CrossRef
  32. Junttila TT, Sundvall M, Määttä JA, Elenius K. Erbb4 and its isoforms: selective regulation of growth factor responses by naturally occurring receptor variants. Trends Cardiovasc Med. 2000;10(7):304-310. PubMed, CrossRef
  33. Zheng Y, Li X, Qian X, Wang Y, Lee JH, Xia Y, Hawke DH, Zhang G, Lyu J, Lu Z. Secreted and O-GlcNAcylated MIF binds to the human EGF receptor and inhibits its activation. Nat Cell Biol. 2015;17(10):1348-1355. PubMed, PubMedCentral, CrossRef
  34. Liao HW, Hsu JM, Xia W, Wang HL, Wang YN, Chang WC, Arold ST, Chou CK, Tsou PH, Yamaguchi H, Fang YF, Lee HJ, Lee HH, Tai SK, Yang MH, Morelli MP, Sen M, Ladbury JE, Chen CH, Grandis JR, Kopetz S, Hung MC. PRMT1-mediated methylation of the EGF receptor regulates signaling and cetuximab response. J Clin Invest. 2015;125(12):4529-4543. PubMed, PubMedCentral, CrossRef
  35. Nanba D, Mammoto A, Hashimoto K, Higashiyama S. Proteolytic release of the carboxy-terminal fragment of proHB-EGF causes nuclear export of PLZF. J Cell Biol. 2003;163(3):489-502. PubMed, PubMedCentral, CrossRef
  36. Kinugasa Y, Hieda M, Hori M, Higashiyama S. The carboxyl-terminal fragment of pro-HB-EGF reverses Bcl6-mediated gene repression. J Biol Chem. 2007;282(20):14797-14806. PubMed, CrossRef
  37. Yeyati PL, Shaknovich R, Boterashvili S, Li J, Ball HJ, Waxman S, Nason-Burchenal K, Dmitrovsky E, Zelent A, Licht JD. Leukemia translocation protein PLZF inhibits cell growth and expression of cyclin A. Oncogene. 1999;18(4):925-934. PubMed, CrossRef
  38. McConnell MJ, Chevallier N, Berkofsky-Fessler W, Giltnane JM, Malani RB, Staudt LM, Licht JD. Growth suppression by acute promyelocytic leukemia-associated protein PLZF is mediated by repression of c-myc expression. Mol Cell Biol. 2003;23(24):9375-9388. PubMed, PubMedCentral, CrossRef
  39. Fernández de Mattos S, Essafi A, Soeiro I, Pietersen AM, Birkenkamp KU, Edwards CS, Martino A, Nelson BH, Francis JM, Jones MC, Brosens JJ, Coffer PJ, Lam EW. FoxO3a and BCR-ABL regulate cyclin D2 transcription through a STAT5/BCL6-dependent mechanism. Mol Cell Biol. 2004;24(22):10058-10071. PubMed, PubMedCentral, CrossRef
  40. Wang F, Sloss C, Zhang X, Lee SW, Cusack JC. Membrane-bound heparin-binding epidermal growth factor like growth factor regulates E-cadherin expression in pancreatic carcinoma cells. Cancer Res. 2007;67(18):8486-8493. PubMed, CrossRef
  41. Alroy I, Yarden Y. The ErbB signaling network in embryogenesis and oncogenesis: signal diversification through combinatorial ligand-receptor interactions. FEBS Lett. 1997;410(1):83-86. PubMed, CrossRef
  42. Muthuswamy SK, Gilman M, Brugge JS. Controlled dimerization of ErbB receptors provides evidence for differential signaling by homo- and heterodimers. Mol Cell Biol. 1999;19(10):6845-6857. PubMed, PubMedCentral, CrossRef
  43. Iwamoto R, Handa K, Mekada E. Contact-dependent growth inhibition and apoptosis of epidermal growth factor (EGF) receptor-expressing cells by the membrane-anchored form of heparin-binding EGF-like growth factor. J Biol Chem. 1999;274(36):25906-25912. PubMed, CrossRef
  44. Chan TO, Rittenhouse SE, Tsichlis PN. AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by phosphoinositide-dependent phosphorylation. Annu Rev Biochem. 1999;68:965-1014. PubMed, CrossRef
  45. Sakuma T, Higashiyama S, Hosoe S, Hayashi S, Taniguchi N. CD9 antigen interacts with heparin-binding EGF-like growth factor through its heparin-binding domain. J Biochem. 1997;122(2):474-480. PubMed, CrossRef
  46. Maecker HT, Todd SC, Levy S. The tetraspanin superfamily: molecular facilitators. FASEB J. 1997;11(6):428-442. PubMed, CrossRef
  47. Lagaudrière-Gesbert C, Le Naour F, Lebel-Binay S, Billard M, Lemichez E, Boquet P, Boucheix C, Conjeaud H, Rubinstein E. Functional analysis of four tetraspans, CD9, CD53, CD81, and CD82, suggests a common role in costimulation, cell adhesion, and migration: only CD9 upregulates HB-EGF activity. Cell Immunol. 1997;182(2):105-112. PubMed, CrossRef
  48. Nakamura K, Mitamura T, Takahashi T, Kobayashi T, Mekada E. Importance of the major extracellular domain of CD9 and the epidermal growth factor (EGF)-like domain of heparin-binding EGF-like growth factor for up-regulation of binding and activity. J Biol Chem. 2000;275(24):18284-18290. PubMed, CrossRef
  49. Symington BE, Takada Y, Carter WG. Interaction of integrins alpha 3 beta 1 and alpha 2 beta 1: potential role in keratinocyte intercellular adhesion. J Cell Biol. 1993;120(2):523-535. PubMed, PubMedCentral, CrossRef
  50. Symington BE, Carter WG. Modulation of epidermal differentiation by epiligrin and integrin alpha 3 beta 1. J Cell Sci. 1995;108(Pt 2):831-838. PubMed, CrossRef
  51. Harris RC, Chung E, Coffey RJ. EGF receptor ligands. Exp Cell Res. 2003;284(1):2-13. PubMed, CrossRef
  52. Raab G, Klagsbrun M. Heparin-binding EGF-like growth factor. Biochim Biophys Acta. 1997;1333(3):F179-F199. PubMed, CrossRef
  53. Higashiyama S, Abraham JA, Klagsbrun M. Heparin-binding EGF-like growth factor stimulation of smooth muscle cell migration: dependence on interactions with cell surface heparan sulfate. J Cell Biol. 1993;122(4):933-940. PubMed, PubMedCentral, CrossRef
  54. Piepkorn M, Pittelkow MR, Cook PW. Autocrine regulation of keratinocytes: the emerging role of heparin-binding, epidermal growth factor-related growth factors. J Invest Dermatol. 1998;111(5):715-721. PubMed, CrossRef
  55. St John T, Meyer J, Idzerda R, Gallatin WM. Expression of CD44 confers a new adhesive phenotype on transfected cells.
    Cell. 1990;60(1):45-52. PubMed, CrossRef
  56. Takemura T, Kondo S, Homma T, Sakai M, Harris RC. The membrane-bound form of heparin-binding epidermal growth factor-like growth factor promotes survival of cultured renal epithelial cells. J Biol Chem. 1997;272(49):31036-31042. PubMed, CrossRef
  57. Lin J, Hutchinson L, Gaston SM, Raab G, Freeman MR. BAG-1 is a novel cytoplasmic binding partner of the membrane form of heparin-binding EGF-like growth factor: a unique role for proHB-EGF in cell survival regulation. J Biol Chem. 2001;276(32):30127-30132. PubMed, CrossRef
  58. Threadgill DW, Dlugosz AA, Hansen LA, Tennenbaum T, Lichti U, Yee D, LaMantia C, Mourton T, Herrup K, Harris RC, et al. Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype. Science. 1995;269(5221):230-234. PubMed, CrossRef
  59. Townsend PA, Cutress RI, Sharp A, Brimmell M, Packham G. BAG-1: a multifunctional regulator of cell growth and survival. Biochim Biophys Acta. 2003;1603(2):83-98. PubMed, CrossRef
  60. Knee DA, Froesch BA, Nuber U, Takayama S, Reed JC. Structure-function analysis of Bag1 proteins. Effects on androgen receptor transcriptional activity. J Biol Chem. 2001;276(16):12718-12724. PubMed, CrossRef
  61. Hague A, Packham G, Huntley S, Shefford K, Eveson JW. Deregulated Bag-1 protein expression in human oral squamous cell carcinomas and lymph node metastases. J Pathol. 2002;197(1):60-71. PubMed, CrossRef
  62. Brooke JS, Cha JH, Eidels L. Latent transforming growth factor beta-binding protein-3 and fibulin-1C interact with the extracellular domain of the heparin-binding EGF-like growth factor precursor. BMC Cell Biol. 2002;3:2. PubMed, PubMedCentral, CrossRef
  63. Fagerberg L, Hallström BM, Oksvold P, Kampf C, Djureinovic D, Odeberg J, Habuka M, Tahmasebpoor S, Danielsson A, Edlund K, Asplund A, Sjöstedt E, Lundberg E, Szigyarto CA, Skogs M, Takanen JO, Berling H, Tegel H, Mulder J, Nilsson P, Schwenk JM, Lindskog C, Danielsson F, Mardinoglu A, Sivertsson A, von Feilitzen K, Forsberg M, Zwahlen M, Olsson I, Navani S, Huss M, Nielsen J, Ponten F, Uhlén M. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics. 2014;13(2):397-406. PubMed, PubMedCentral, CrossRef
  64. Ito N, Kawata S, Tamura S, Kiso S, Tsushima H, Damm D, Abraham JA, Higashiyama S, Taniguchi N, Matsuzawa Y. Heparin-binding EGF-like growth factor is a potent mitogen for rat hepatocytes. Biochem Biophys Res Commun. 1994;198(1):25-31. PubMed, CrossRef
  65. Miyamoto S, Hirata M, Yamazaki A, Kageyama T, Hasuwa H, Mizushima H, Tanaka Y, Yagi H, Sonoda K, Kai M, Kanoh H, Nakano H, Mekada E. Heparin-binding EGF-like growth factor is a promising target for ovarian cancer therapy. Cancer Res. 2004;64(16):5720-5727. PubMed, CrossRef
  66. Tanaka Y, Miyamoto S, Suzuki SO, Oki E, Yagi H, Sonoda K, Yamazaki A, Mizushima H, Maehara Y, Mekada E, Nakano H. Clinical significance of heparin-binding epidermal growth factor-like growth factor and a disintegrin and metalloprotease 17 expression in human ovarian cancer. Clin Cancer Res. 2005;11(13):4783-4792. PubMed, CrossRef
  67. Blotnick S, Peoples GE, Freeman MR, Eberlein TJ, Klagsbrun M. T lymphocytes synthesize and export heparin-binding epidermal growth factor-like growth factor and basic fibroblast growth factor, mitogens for vascular cells and fibroblasts: differential production and release by CD4+ and CD8+ T cells. Proc Natl Acad Sci USA. 1994;91(8):2890-2894. PubMed, PubMedCentral, CrossRef
  68. Chapellier B, Mark M, Messaddeq N, Calléja C, Warot X, Brocard J, Gérard C, Li M, Metzger D, Ghyselinck NB, Chambon P. Physiological and retinoid-induced proliferations of epidermis basal keratinocytes are differently controlled. EMBO J. 2002;21(13):3402-3413. PubMed, PubMedCentral, CrossRef
  69. Rodero MP, Khosrotehrani K. Skin wound healing modulation by macrophages. Int J Clin Exp Pathol. 2010;3(7):643-653. PubMed, PubMedCentral
  70. Galkin OYu, Besarab AB, Lutsenko TN. Characteristics of enzyme-linked immunosorbent assay for detection of IgG antibodies specific to Сhlamydia trachomatis heat shock protein (HSP-60). Ukr Biochem J. 2017;89(1):22-30. CrossRef
  71. Homma T, Sakai M, Cheng HF, Yasuda T, Coffey RJ Jr, Harris RC. Induction of heparin-binding epidermal growth factor-like growth factor mRNA in rat kidney after acute injury. J Clin Invest. 1995;96(2):1018-1025. PubMed, PubMedCentral, CrossRef
  72. Kang LI, Mars WM, Michalopoulos GK. Signals and cells involved in regulating liver regeneration. Cells. 2012;1(4):1261-1292. PubMed, PubMedCentral, CrossRef
  73. Grigorieva SM, Starosyla DB, Rybalko SL, Motronenko VV, Lutsenko TM, Galkin OY. Effect of recombinant human interleukin-7 on Pseudomonas aeruginosa wound infection. Ukr Biochem J. 2019;91(5):7-15. CrossRef
  74. Choi N, Kim WS, Oh SH, Sung JH. HB-EGF Improves the Hair Regenerative Potential of Adipose-Derived Stem Cells via ROS Generation and Hck Phosphorylation. Int J Mol Sci. 2019;21(1):122. PubMed, PubMedCentral, CrossRef
  75. Wang YJ, Dou J, Cross KP, Valerio LG Jr. Computational analysis for hepatic safety signals of constituents present in botanical extracts widely used by women in the United States for treatment of menopausal symptoms. Regul Toxicol Pharmacol. 2011;59(1):111-124. PubMed, CrossRef
  76. Goltsev A, Bondarovych M, Gaevska Y, Dubrava T, Babenko N, Ostankov M. Modern methods of obtaining immune dendritic cells with anti-tumor potential. Innov Biosyst Bioeng. 2024;8(1):56-76. CrossRef
  77. Long DL, Ulici V, Chubinskaya S, Loeser RF. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is increased in osteoarthritis and regulates chondrocyte catabolic and anabolic activities. Osteoarthritis Cartilage. 2015;23(9):1523-1531. PubMed, PubMedCentral, CrossRef
  78. Basal O, Atay T, Ciris İM, Baykal YB. Epidermal growth factor (EGF) promotes bone healing in surgically induced osteonecrosis of the femoral head (ONFH). Bosn J Basic Med Sci. 2018;18(4):352-360. PubMed, PubMedCentral, CrossRef
  79. Mehta VB, Besner GE. HB-EGF promotes angiogenesis in endothelial cells via PI3-kinase and MAPK signaling pathways. Growth Factors. 2007;25(4):253-263. PubMed, CrossRef
  80. Rocourt DV, Mehta VB, Besner GE. Heparin-binding EGF-like growth factor decreases inflammatory cytokine expression after intestinal ischemia/reperfusion injury. J Surg Res. 2007;139(2):269-273. PubMed, PubMedCentral, CrossRef
  81. Ljubimov AV, Saghizadeh M. Progress in corneal wound healing. Prog Retin Eye Res. 2015;49:17-45. PubMed, PubMedCentral, CrossRef
  82. Xu KP, Yin J, Yu FS. Lysophosphatidic acid promoting corneal epithelial wound healing by transactivation of epidermal growth factor receptor. Invest Ophthalmol Vis Sci. 2007;48(2):636-643. PubMed, PubMedCentral, CrossRef
  83. Soloviov S, Trokhimenko O, Polishchuk V, Pits V, Vasylenko V, Vasylenko Y, Hol I, Symchuk A, Kostiuk O. In vitro modeling of the effect of lactobacillus metabolites on the systemic response of the body in intestinal viral infection. Innov Biosyst Bioeng. 2024;8(2):38-52. CrossRef
  84. Galkin A, Komar A, Gorshunov Y, Besarab A, Soloviova V. New monoclonal antibodies to the prostate-specific antigen: obtaining and studying biological properties. J Microbiol Biotech Food Sci. 2019;9(3):573-577. CrossRef
  85. 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.
    PubMed, PubMedCentral, CrossRef
  86. Cheng WL, Feng PH, Lee KY, Chen KY, Sun WL, Van Hiep N, Luo CS, Wu SM. The Role of EREG/EGFR Pathway in Tumor Progression. Int J Mol Sci. 2021;22(23):12828. PubMed, PubMedCentral, CrossRef
Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.